Glycoprotein Hormone Receptors - TSHR, FSHR, LHCGR (LHR)

PostHeaderIcon Focussed Literature

Topics

Glycosylation Cysteine-box 1 ECL 1 TMHs 1-7 Reviews Small Molecules
Promiscuous
Hormone Binding
LRRD /
Hormone Binding
ECL 2 Molecular Models Superactive
GPH analogues
Cleavage and
Shedding
Cysteine-box 2 ECL 3 Thyrostimulin
Interplay
ECD/SD
LHCGR - Exon10 ICL 1 LGRs
Dimerization Cysteine-box 2/3
linker region
ICL 2 Extrathyroidal TSHR
Ionic
influence
Cysteine-box 3 ICL 3

Reviews

TSHR

Hebrant A, van Staveren WC, Maenhaut C, Dumont JE, Leclere J.
Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations.
Eur J Endocrinol. 2011 Jan;164(1):1-9
Pubmed

Persani L, Calebiro D, Cordella D, Weber G, Gelmini G, Libri D, de Filippis T, Bonomi M
Genetics and phenomics of hypothyroidism due to TSH resistance.
Mol Cell Endocrinol. 2010 Jun 30;322(1-2):72-82
Pubmed

Paus R.
Exploring the "thyroid-skin connection": concepts, questions, and clinical relevance.
J Invest Dermatol. 2010 Jan;130(1):7-10
Pubmed

Biebermann H, Winkler F, Kleinau G.
Genetic defects, thyroid growth and malfunctions of the TSHR in pediatric patients.
Front Biosci. 2010 Jun 1;15:913-33
Pubmed

Kleinau G, Krause G.
Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms.
Endocr Rev. 2009 Apr;30(2):133-51.
Pubmed

Latif R, Morshed SA, Zaidi M, Davies TF.
The thyroid-stimulating hormone receptor: impact of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on multimerization, cleavage, and signaling.
Endocrinol Metab Clin North Am. 2009 Jun;38(2):319-41, viii.
Pubmed

Michalek K, Morshed SA, Latif R, Davies TF
TSH receptor autoantibodies
Autoimmun Rev. 2009 Dec;9(2):113-6. Epub 2009 Mar 27
Pubmed

Kim CS, Zhu X
Lessons from mouse models of thyroid cancer.
Thyroid. 2009 Dec;19(12):1317-31.
Pubmed

Haugen BR.
Drugs that suppress TSH or cause central hypothyroidism.
Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):793-800
Pubmed

Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L.
The specificity of binding of glycoprotein hormones to their receptors.
Cell Mol Life Sci. 2008 Aug;65(16):2484-92
Pubmed

García-Jiménez C, Santisteban P.
TSH signalling and cancer.
Arq Bras Endocrinol Metabol. 2007 Jul;51(5):654-71
Pubmed

Rapoport B, McLachlan SM
The thyrotropin receptor in Graves' disease
Thyroid. 2007 Oct;17(10):911-22
Pubmed

Holger Jaeschke, Maren Claus, Gunnar Kleinau, Gerd Krause, Ralf Paschke
TSH-RECEPTOR STRUCTURE AND MECHANISM OF ACTIVATION
HOT THYROIDOLOGY (www.hotthyroidology.com), May, No 1, 2005
Link

Terry F. Davies, Takao Ando, Reigh-Yi Lin, Yaron Tomer, and Rauf Latif
Thyrotropin receptor–associated diseases: from adenomata to Graves disease
J Clin Invest. 2005 August 1; 115(8): 1972–1983
Pubmed

Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M, Kretsinger RH
Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases.
Cell Mol Life Sci. 2005 Dec;62(23):2771-91
Pubmed

Vassart G, Pardo L, Costagliola S
A molecular dissection of the glycoprotein hormone receptors
Trends Biochem Sci. 2004 Mar;29(3):119-26
Pubmed

Gruters A, Krude H, Biebermann H
Molecular genetic defects in congenital hypothyroidism
Eur J Endocrinol. 2004 Nov;151 Suppl 3:U39-44
Pubmed

Rodien P, Ho SC, Vlaeminck V, Vassart G, Costagliola S
Activating mutations of TSH receptor
Ann Endocrinol (Paris). 2003 Feb;64(1):12-6
Pubmed

Szkudlinski MW, Fremont V, Ronin C, Weintraub BD
Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships
Physiol Rev. 2002 Apr;82(2):473-502
Pubmed

Corvilain B, Van Sande J, Dumont JE, Vassart G
Somatic and germline mutations of the TSH receptor and thyroid diseases
Clin Endocrinol (Oxf). 2001 Aug;55(2):143-58
Pubmed

Wonerow P, Neumann S, Gudermann T, Paschke R
Thyrotropin receptor mutations as a tool to understand thyrotropin receptor action
J Mol Med. 2001 Dec;79(12):707-21
Pubmed

Szkudlinski MW, Grossmann M, Leitolf H, Weintraub BD
Human Thyroid-Stimulating Hormone: Structure-Function Analysis
Methods. 2000 May;21(1):67-81
Pubmed

Farid NR, Kascur V, Balazs C
The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations
Eur J Endocrinol. 2000 Jul;143(1):25-30
Pubmed

Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM
The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies
Endocr Rev. 1998 Dec;19(6):673-716
Pubmed

Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G
The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):116-20
Pubmed

Kosugi S, Sugawa H, Mori T
TSH receptor and LH receptor, 1996
Endocr J. 1996 Dec;43(6):595-604
Pubmed

FSHR

Kleinau G, Krause G.
Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms.
Endocr Rev. 2009 Apr;30(2):133-51.
Pubmed

Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L.
The specificity of binding of glycoprotein hormones to their receptors.
Cell Mol Life Sci. 2008 Aug;65(16):2484-92
Pubmed

Jeoung M, Lee C, Ji I, Ji TH
Trans-activation, cis-activation and signal selection of gonadotropin receptors.
Mol Cell Endocrinol. 2007 Jan 2;260-262:137-43
Pubmed

Gromoll J, Simoni M
Genetic complexity of FSH receptor function
Trends Endocrinol Metab. 2005 Oct;16(8):368-73
Pubmed

Themmen, A. P N.
Focus on Gonadotrophin Signalling An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms
Reproduction (2005) 130 263-274
Link

Costagliola S, Urizar E, Mendive F, Vassart G
Specificity and promiscuity of gonadotropin receptors
Reproduction. 2005 Sep;130(3):275-81
Pubmed

Dias JA.
Endocrinology: fertility hormone in repose.
Nature. 2005 Jan 20;433(7023):203-4
Pubmed

Vassart G, Pardo L, Costagliola S
A molecular dissection of the glycoprotein hormone receptors
Trends Biochem Sci. 2004 Mar;29(3):119-26
Pubmed

Dias JA, Cohen BD, Lindau-Shepard B, Nechamen CA, Peterson AJ, Schmidt A
Molecular, structural, and cellular biology of follitropin and follitropin receptor
Vitam Horm. 2002;64:249-322
Pubmed

Yi CS, Song YS, Ryu KS, Sohn J, Ji I, Ji TH
Common and differential mechanisms of gonadotropin receptors
Cell Mol Life Sci. 2002 Jun;59(6):932-40
Pubmed

Dias JA, Van Roey P
Structural Biology of Human Follitropin and Its Receptor
Arch Med Res. 2001 Nov-Dec;32(6):510-9
Pubmed

Themmen APN, Huhtaniemi IT
Mutations of Gonadotropin and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function
Endocr Rev. 2000 Oct;21(5):551-83
Pubmed

Levallet J, Pakarinen P, Huhtaniemi IT
Follicle-Stimulating Hormone Ligand and Receptor Mutations, and Gonadal Dysfunction
Arch Med Res. 1999 Nov-Dec;30(6):486-94
Pubmed

Simoni M, Gromoll J, Nieschlag E
The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology
Endocr Rev. 1997 Dec;18(6):739-73
Pubmed

Gromoll J, Simoni M, Nordhoff V, Behre HM, De Geyter C, Nieschlag E
Functional and clinical consequences of mutations in the FSH receptor
Mol Cell Endocrinol. 1996 Dec 20;125(1-2):177-82
Pubmed

LHCGR

Segaloff DL.
Constitutive activity of the lutropin receptor and its allosteric modulation by receptor heterodimerization.
Methods Enzymol. 2010;484:231-52.
Pubmed

Kleinau G, Krause G.
Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms.
Endocr Rev. 2009 Apr;30(2):133-51.
Pubmed

Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L.
The specificity of binding of glycoprotein hormones to their receptors.
Cell Mol Life Sci. 2008 Aug;65(16):2484-92
Pubmed

Puett D, Li Y, Demars G, Angelova K, Fanelli F.
A functional transmembrane complex: The luteinizing hormone receptor with bound ligand and G protein
Mol Cell Endocrinol. 2007 Jan 2;260-262:126-36.
Pubmed

Jeoung M, Lee C, Ji I, Ji TH
Trans-activation, cis-activation and signal selection of gonadotropin receptors.
Mol Cell Endocrinol. 2007 Jan 2;260-262:137-43
Pubmed

Themmen, A. P N.
Focus on Gonadotrophin Signalling An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms
Reproduction (2005) 130 263-274
Link

Puett D, Li Y, Angelova K, Demars G, Meehan TP, Fanelli F, Narayan P
Structure-function relationships of the luteinizing hormone receptor.
Ann N Y Acad Sci. 2005 Dec;1061:41-54
Pubmed

Vassart G, Pardo L, Costagliola S
A molecular dissection of the glycoprotein hormone receptors
Trends Biochem Sci. 2004 Mar;29(3):119-26
Pubmed

Shenker A
Activating mutations of the lutropin choriogonadotropin receptor in precocious puberty
Receptors Channels, 2002;8(1):3-18
Pubmed

Ascoli M, Fanelli F, Segaloff DL
The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective
Endocr Rev. 2002 Apr;23(2):141-74
Pubmed

Yi CS, Song YS, Ryu KS, Sohn J, Ji I, Ji TH
Common and differential mechanisms of gonadotropin receptors
Cell Mol Life Sci. 2002 Jun;59(6):932-40
Pubmed

Themmen APN, Huhtaniemi IT
Mutations of Gonadotropin and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function
Endocr Rev. 2000 Oct;21(5):551-83
Pubmed

Dufau ML
The luteinizing hormone receptor
Annu Rev Physiol. 1998;60:461-96
Pubmed

Kosugi S, Sugawa H, Mori T
TSH receptor and LH receptor, 1996
Endocr J. 1996 Dec;43(6):595-604
Pubmed

Cysteine-box 1

Ji I, Lee C, Jeoung M, Koo Y, Sievert GA, Ji TH
Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals
Mol Endocrinol. 2004 Apr;18(4):968-78
Pubmed

Piotrowska U, Adler G, Kilianski J
Residues 34-39 in the thyrotropin receptor are not the target of autoantibodies from sera of patients with Graves' disease
Endocr Res. 2004 Aug;30(3):431-41
Pubmed

Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface
J Biol Chem. 2004 Dec 3;279(49):51590-600
Pubmed

Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH
Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3
J Biol Chem. 2003 Nov 28;278(48):47868-76
Pubmed

Zhang R, Buczko E, Dufau ML
Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding
J Biol Chem. 1996 Mar 8;271(10):5755-60
Pubmed

Gustavsson B, Eklof C, Westermark K, Westermark B, Heldin NE
Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease
Mol Cell Endocrinol 1995 Jun;111(2):167-73
Pubmed

Wadsworth HL, Russo D, Nagayama Y, Chazenbalk GD, Rapoport B
Studies on the role of amino acids 38-45 in the expression of a functional thyrotropin receptor
Mol Endocrinol 1992 Mar;6(3):394-8
Pubmed

LRRD / Hormone binding

Chen CR, McLachlan SM, Rapoport B.
Thyrotropin (TSH) receptor residue E251 in the extracellular leucine-rich repeat domain is critical for linking TSH binding to receptor activation.
Endocrinology. 2010 Apr;151(4):1940-7
Pubmed

Angelova K, de Jonge H, Granneman JC, Puett D, Bogerd J
Functional differences of invariant and highly conserved residues in the extracellular domain of the glycoprotein hormone receptors.
J Biol Chem. 2010 Nov 5;285(45):34813-27.
Pubmed

Chen CR, McLachlan SM, Rapoport B
IDENTIFICATION OF KEY AMINO ACID RESIDUES IN A THYROTROPIN RECEPTOR MONOCLONAL ANTIBODY EPITOPE PROVIDES INSIGHT INTO ITS INVERSE AGONIST AND ANTAGONIST PROPERTIES.
Endocrinology. 2008 Jul;149(7):3427-34
Pubmed

Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L.
The specificity of binding of glycoprotein hormones to their receptors.
Cell Mol Life Sci. 2008 Aug;65(16):2484-92
Pubmed

Royer J, Lefevre-Minisini A, Caltabiano G, Lacombe T, Malthiery Y, Savagner F, Pardo L, Rodien P.
The cloned equine thyrotropin receptor is hypersensitive to human chorionic gonadotropin; identification of three residues in the extracellular domain involved in ligand specificity.
Endocrinology. 2008 Oct;149(10):5088-96
Pubmed

Lin W, Bernard MP, Cao D, Myers RV, Kerrigan JE, Moyle WR
Follitropin receptors contain cryptic ligand binding sites.
Mol Cell Endocrinol. 2007 Jan 2;260-262:83-92
Pubmed

Fan QR, Hendrickson WA
Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor.
Mol Cell Endocrinol. 2007 Jan 2;260-262:73-82.
Pubmed

Bogerd J
Ligand-selective determinants in gonadotropin receptors
Mol Cell Endocrinol. 2007 Jan 2;260-262:144-52
Pubmed

Sanders J, Bolton J, Sanders P, Jeffreys J, Nakatake N, Richards T, Evans M, Kiddie A, Summerhayes S, Roberts E, Miguel RN, Furmaniak J, Smith BR
Effects of TSH receptor mutations on binding and biological activity of monoclonal antibodies and TSH.
Thyroid. 2006 Dec;16(12):1195-206
Pubmed

Fan QR, Hendrickson WA
Structure of human follicle-stimulating hormone in complex with its receptor
Nature. 2005 Jan 20;433(7023):203-4
Pubmed

Galet C, Ascoli M
The differential binding affinities of the luteinizing hormone (LH)/choriogonadotropin receptor for LH and choriogonadotropin are dictated by different extracellular domain residues
Mol Endocrinol. 2005 May;19(5):1263-76
Pubmed

Fan QR, Hendrickson WA
Structural biology of glycoprotein hormones and their receptors
Endocrine. 2005 Apr;26(3):179-88
Pubmed

Dias JA.
Endocrinology: fertility hormone in repose.
Nature. 2005 Jan 20;433(7023):203-4
Pubmed

Gudermann T, Nurwakagari P, Ben-Menahem D
Hormone binding to the follicle-stimulating hormone receptor--crystal clear!
Exp Clin Endocrinol Diabetes. 2005 May;113(5):245-7
Pubmed

Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M, Kretsinger RH
Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases
Cell Mol Life Sci. 2005 Dec;62(23):2771-91
Pubmed

Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface
J Biol Chem. 2004 Dec 3;279(49):51590-600
Pubmed

Vischer HF, Granneman JC, Noordam MJ, Mosselman S, Bogerd J
Ligand selectivity of gonadotropin receptors. Role of the beta-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor
J Biol Chem. 2003 May 2;278(18):15505-13
Pubmed

Smits G, Campillo M, Govaerts C, Janssens V, Richter C, Vassart G, Pardo L, Costagliola S
Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity
EMBO J., 2003 Jun 2;22(11):2692-703S
Pubmed

Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH
Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3
J Biol Chem. 2003 Nov 28;278(48):47868-76
Pubmed

Bhowmick N, Narayan P, Puett D
Identification of ionizable amino acid residues on the extracellular domain of the lutropin receptor involved in ligand binding
Endocrinology. 1999 Oct;140(10):4558-63
Pubmed

Hong S, Phang T, Ji I, Ji TH
The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. I. Mutational analysis
J Biol Chem. 1998 May 29;273(22):13835-40
Pubmed

Bhowmick N, Huang J, Puett D, Isaacs NW, Lapthorn AJ
Determination of residues important in hormone binding to the extracellular domain of the luteinizing hormone/chorionic gonadotropin receptor by site-directed mutagenesis and modeling.
Mol Endocrinol. 1996 Sep;10(9):1147-59
Pubmed

Nagayama Y, Yamasaki H, Takeshita A, Kimura H, Ashizawa K, Yokoyama N, Yamashita S, Rapoport B, Nagataki S.
Thyrotropin binding specificity for the thyrotropin receptor.
J Endocrinol Invest. 1995 Apr;18(4):283-7
Pubmed

Moyle WR, Campbell RK, Myers RV, Bernard MP, Han Y, Wang X.
Co-evolution of ligand-receptor pairs.
Nature. 1994 Mar 17;368(6468):251-5
Pubmed

Nagayama Y, Wadsworth HL, Chazenbalk GD, Russo D, Seto P, Rapoport B.
Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function.
Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):902-5.
Pubmed

Nagayama Y, Russo D, Wadsworth HL, Chazenbalk GD, Rapoport B.
Eleven amino acids (Lys-201 to Lys-211) and 9 amino acids (Gly-222 to Leu-230) in the human thyrotropin receptor are involved in ligand binding.
J Biol Chem. 1991 Aug 15;266(23):14926-30.
Pubmed

Cysteine-box 2

Mueller S, Kleinau G, Szkudlinski MW, Jaeschke H, Krause G, Paschke R
The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor
J Biol Chem. 2009 Jun 12;284(24):16317-24. Epub 2009 Apr 22
Pubmed

Mizutori Y, Chen CR, McLachlan SM, Rapoport B.
The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction.
Mol Endocrinol. 2008 May;22(5):1171-82
Pubmed

Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G.
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
J Biol Chem. 2008 Jun 27;283(26):18048-55
Pubmed

Bruysters M, Verhoef-Post M, Themmen AP.
Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation.
J Biol Chem. 2008 Sep 19;283(38):25821-8.
Pubmed

Ho SC, Goh SS, Li S, Khoo DH, Paterson M
Effects of mutations involving cysteine residues distal to the S281HCC motif at the C-terminus on the functional characteristics of a truncated ectodomain-only thyrotropin receptor anchored on glycosylphosphatidyl-inositol.
Thyroid. 2008 Dec;18(12):1313-9
Pubmed

Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R
An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function
Endocrinology. 2006 Apr;147(4):1753-60
Pubmed

Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R.
Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor.
J Biol Chem. 2006 Oct 20;281(42):31638-46.
Pubmed

Neumann S, Claus M, Paschke R
Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation
Eur J Endocrinol. 2005 Apr;152(4):625-34
Pubmed

Ho SC, Goh SS, Su Q, Khoo DH
Cysteine 390 mutation of the TSH receptor modulates its ectodomain as an inverse agonist on the serpentine domain with decrease in basal constitutive activity
Mol Cell Endocrinol. 2005 Dec 21;245(1-2):158-68
Pubmed

Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface
J Biol Chem. 2004 Dec 3;279(49):51590-600
Pubmed

Nakabayashi K, Kudo M, Hsueh AJ, Maruo T
Activation of the luteinizing hormone receptor in the extracellular domain
Mol Cell Endocrinol. 2003 Apr 28;202(1-2):139-44
Pubmed

Nishi S, Nakabayashi K, Kobilka B, Hsueh AJ
The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region: studies using chimeric human and fly receptors
J Biol Chem. 2002 Feb 8;277(6):3958-64
Pubmed

Sangkuhl K, Schulz A, Schultz G, Schoneberg T
Structural requirements for mutational lutropin/choriogonadotropin receptor activation
J Biol Chem. 2002 Dec 6;277(49):47748-55
Pubmed

Ho SC, Van Sande J, Lefort A, Vassart G, Costagliola S
Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity
Endocrinology. 2001 Jul;142(7):2760-7
Pubmed

Zeng H, Phang T, Song YS, Ji I, Ji TH
The role of the hinge region of the luteinizing hormone receptor in hormone interaction and signal generation
J Biol Chem. 2001 Feb 2;276(5):3451-8
Pubmed

Nakabayashi K, Kudo M, Kobilka B, Hsueh AJ
Activation of the luteinizing hormone receptor following substitution of Ser-277 with selective hydrophobic residues in the ectodomain hinge region
J Biol Chem. 2000 Sep 29;275(39):30264-71
Pubmed

Bernard MP, Myers RV, Moyle WR
Lutropins appear to contact two independent sites in the extracellular domain of their receptors.
Biochem J. 1998 Nov 1;335 ( Pt 3):611-7
Pubmed

Duprez L, Parma J, Costagliola S, Hermans J, Van Sande J, Dumont JE, Vassart G
Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain.
FEBS Lett. 1997 Jun 16;409(3):469-74
Pubmed

Zhang R, Buczko E, Dufau ML
Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding
J Biol Chem. 1996 Mar 8;271(10):5755-60
Pubmed

Akamizu T, Inoue D, Kosugi S, Kohn LD, Mori T
Further studies of amino acids (268-304) in thyrotropin (TSH)--lutropin/chorionic gonadotropin (LH/CG) receptor chimeras: cysteine-301 is important in TSH binding and receptor tertiary structure
Thyroid. 1994 Spring;4(1):43-8
Pubmed

Nagayama Y, Rapoport B.
Role of the carboxyl-terminal half of the extracellular domain of the human thyrotropin receptor in signal transduction.
Endocrinology. 1992 Aug;131(2):548-52.
Pubmed

LHCGR - Exon 10

Scammell JG, Funkhouser JD, Moyer FS, Gibson SV, Willis DL
Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey
Gen Comp Endocrinol. 2008 Feb 1;155(3):534-41
Pubmed

Gromoll J, Lahrmann L, Godmann M, Müller T, Michel C, Stamm S, Simoni M
Genomic checkpoints for exon 10 usage in the luteinizing hormone receptor type 1 and type 2
Mol Endocrinol. 2007 Aug;21(8):1984-96
Pubmed

Michel C, Gromoll J, Chandolia R, Luetjens CM, Wistuba J, Simoni M
LHR splicing variants and gene expression in the marmoset monkey
Mol Cell Endocrinol. 2007 Dec 15;279(1-2):9-15
Pubmed

Muller T, Simoni M, Pekel E, Luetjens CM, Chandolia R, Amato F, Norman RJ, Gromoll J
Chorionic gonadotrophin beta subunit mRNA but not luteinising hormone beta subunit mRNA is expressed in the pituitary of the common marmoset (Callithrix jacchus)
J Mol Endocrinol. 2004 Feb;32(1):115-28
Pubmed

Muller T, Gromoll J, Simula AP, Norman R, Sandhowe-Klaverkamp R, Simoni M
The carboxyterminal peptide of chorionic gonadotropin facilitates activation of the marmoset LH receptor
Exp Clin Endocrinol Diabetes. 2004 Nov;112(10):574-9
Pubmed

Mueller T, Gromoll J, Simoni M
Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action
J Clin Endocrinol Metab. 2003 May;88(5):2242-9
Pubmed

Gromoll J, Wistuba J, Terwort N, Godmann M, Muller T, Simoni M
A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the New World monkey (Platyrrhini) lineage
Biol Reprod. 2003 Jul;69(1):75-80
Pubmed

Gromoll J, Eiholzer U, Nieschlag E, Simoni M
Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH
J Clin Endocrinol Metab. 2000 Jun;85(6):2281-6
Pubmed

Glycosylation

Clouser CL, Menon KM
N-linked glycosylation facilitates processing and cell surface expression of rat luteinizing hormone receptor.
Mol Cell Endocrinol. 2005 May 12;235(1-2):11-9
Pubmed

Frenzel R, Krohn K, Eszlinger M, Tonjes A, Paschke R
Sialylation of human thyrotropin receptor improves and prolongs its cell-surface expression.
Mol Pharmacol. 2005 Oct;68(4):1106-13
Pubmed

Nagayama Y, Nishihara E, Namba H, Yamashita S, Niwa M
Identification of the sites of asparagine-linked glycosylation on the human thyrotropin receptor and studies on their role in receptor function and expression
J Pharmacol Exp Ther. 2000 Oct;295(1):404-9
Pubmed

Oda Y, Sanders J, Roberts S, Maruyama M, Kiddie A, Furmaniak J, Smith BR
Analysis of carbohydrate residues on recombinant human thyrotropin receptor.
J Clin Endocrinol Metab. 1999 Jun;84(6):2119-25
Pubmed

Davis DP, Rozell TG, Liu X, Segaloff DL
The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction
Mol Endocrinol. 1997 May;11(5):550-62
Pubmed

Schaaf L, Leiprecht A, Saji M, Hübner U, Usadel KH, Kohn LD
Glycosylation variants of human TSH selectively activate signal transduction pathways.
Mol Cell Endocrinol. 1997 Sep 19;132(1-2):185-94.
Pubmed

Zhang R, Cai H, Fatima N, Buczko E, Dufau ML
Functional glycosylation sites of the rat luteinizing hormone receptor required for ligand binding
J Biol Chem. 1995 Sep 15;270(37):21722-8
Pubmed

Davis D, Liu X, Segaloff DL
Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function
Mol Endocrinol. 1995 Feb;9(2):159-70
Pubmed

Russo D, Chazenbalk GD, Nagayama Y, Wadsworth HL, Rapoport B
Site-directed mutagenesis of the human thyrotropin receptor: role of asparagine-linked oligosaccharides in the expression of a functional receptor
Mol Endocrinol. 1991 Jan;5(1):29-33
Pubmed

Zhang R, Tsai-Morris CH, Kitamura M, Buczko E, Dufau ML
Changes in binding activity of luteinizing hormone receptors by site directed mutagenesis of potential glycosylation sites
Biochem Biophys Res Commun. 1991 Dec 16;181(2):804-8
Pubmed

Cleavage and Shedding

Hamidi S, Chen CR, Mizutori-Sasai Y, McLachlan SM, Rapoport B
Relationship between thyrotropin receptor hinge region proteolytic posttranslational modification and receptor physiological function.
Mol Endocrinol. 2011 Jan;25(1):184-94.
Pubmed

Vu MT, Radu A, Ghinea N.
The cleavage of Thyroid-Stimulating Hormone receptor is dependent on cell-cell contacts and regulates the hormonal stimulation of phospholipase C.
J Cell Mol Med. 2009 Aug;13(8B):2253-60.
Pubmed

Kaczur V, Puskas LG, Nagy ZU, Miled N, Rebai A, Juhasz F, Kupihar Z, Zvara A, Hackler L Jr, Farid NR
Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin.
J Mol Recognit. 2007 Sep-Oct;20(5):392-404
Pubmed

Chen CR, Chazenbalk GD, Wawrowsky KA, McLachlan SM, Rapoport B
Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface.
Endocrinology. 2006 Jun;147(6):3107-13
Pubmed

Chazenbalk GD, Chen CR, McLachlan SM, Rapoport B
Does thyrotropin cleave its cognate receptor?
Endocrinology. 2004 Jan;145(1):4-10
Pubmed

Vassart G, Costagliola S
A physiological role for the posttranslational cleavage of the thyrotropin receptor?
Endocrinology. 2004 Jan;145(1):1-3
Pubmed

Latif R, Ando T, Davies TF
Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor
Endocrinology. 2004 Dec;145(12):5580-8
Pubmed

Chen CR, Chazenbalk GD, McLachlan SM, Rapoport B
Targeted restoration of cleavage in a noncleaving thyrotropin receptor demonstrates that cleavage is insufficient to enhance ligand-independent activity
Endocrinology. 2003 Apr;144(4):1324-30
Pubmed

Ciullo I, Latif R, Graves P, Davies TF
Functional assessment of the thyrotropin receptor-beta subunit
Endocrinology. 2003 Jul;144(7):3176-81
Pubmed

Quellari M, Desroches A, Beau I, Beaudeux E, Misrahi M
Role of cleavage and shedding in human thyrotropin receptor function and trafficking
Eur J Biochem. 2003 Sep;270(17):3486-97
Pubmed

Chen CR, Chazenbalk GD, McLachlan SM, Rapoport B
Evidence that the C terminus of the A subunit suppresses thyrotropin receptor constitutive activity
Endocrinology. 2003 Sep;144(9):3821-7
Pubmed

Chazenbalk GD, McLachlan SM, Chen CR, Rapoport B
Insight into thyrotropin receptor cleavage by engineering the single polypeptide chain luteinizing hormone receptor into a cleaving, two subunit receptor
Eur J Biochem. 2001 Apr;268(8):2261-9
Pubmed

Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B
Evidence that cleavage of the thyrotropin receptor involves a "molecular ruler" mechanism: deletion of amino acid residues 305-320 causes a spatial shift in cleavage site 1 independent of amino acid motif
Endocrinology. 2000 Oct;141(10):3573-7
Pubmed

de Bernard S, Misrahi M, Huet JC, Beau I, Desroches A, Loosfelt H, Pichon C, Pernollet JC, Milgrom E
Sequential cleavage and excision of a segment of the thyrotropin receptor ectodomain
J Biol Chem. 1999 Jan 1;274(1):101-7
Pubmed

Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B
The shed thyrotropin receptor is primarily a carboxyl terminal truncated form of the A subunit, not the entire A subunit
Mol Cell Endocrinol. 1999 Apr 25;150(1-2):113-9
Pubmed

Chazenbalk GD, Tanaka K, McLachlan SM, Rapoport B.
On the functional importance of thyrotropin receptor intramolecular cleavage.
Endocrinology. 1999 Oct;140(10):4516-20
Pubmed

Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B
Thyrotropin receptor cleavage at site 1 does not involve a specific amino acid motif but instead depends on the presence of the unique, 50 amino acid insertion
J Biol Chem. 1998 Jan 23;273(4):1959-63
Pubmed

Chazenbalk GD, Tanaka K, Nagayama Y, Kakinuma A, Jaume JC, McLachlan SM, Rapoport B
Evidence that the thyrotropin receptor ectodomain contains not one, but two, cleavage sites
Endocrinology. 1997 Jul;138(7):2893-9
Pubmed

Kakinuma A, Chazenbalk GD, Tanaka K, Nagayama Y, McLachlan SM, Rapoport B
An N-linked glycosylation motif from the noncleaving luteinizing hormone receptor substituted for the homologous region (Gly367 to Glu369) of the thyrotropin receptor prevents cleavage at its second, downstream site
J Biol Chem. 1997 Nov 7; 272(45): 28296-300
Pubmed

Misrahi M, Milgrom E
Cleavage and shedding of the TSH receptor
Eur J Endocrinol. 1997 Dec;137(6):599-602
Pubmed

Couet J, Sar S, Jolivet A, Hai MT, Milgrom E, Misrahi M
Shedding of human thyrotropin receptor ectodomain. Involvement of a matrix metalloprotease
J Biol Chem. 1996 Feb 23;271(8):4545-52
Pubmed

Van Sande J, Massart C, Costagliola S, Allgeier A, Cetani F, Vassart G, Dumont JE
Specific activation of the thyrotropin receptor by trypsin
Mol Cell Endocrinol. 1996 May 31;119(2):161-8
Pubmed

Couet J, de Bernard S, Loosfelt H, Saunier B, Milgrom E, Misrahi M
Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain
Biochemistry. 1996 Nov 26;35(47):14800-5
Pubmed

Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E
Two-subunit structure of the human thyrotropin receptor
Proc Natl Acad Sci U S A. 1992 May 1;89(9):3765-9
Pubmed

Cysteine-box 2/3 linker region

Hamidi S, Chen CR, Mizutori-Sasai Y, McLachlan SM, Rapoport B.
Relationship between Thyrotropin Receptor Hinge Region Proteolytic Posttranslational Modification and Receptor Physiological Function.
Mol Endocrinol. 2011 Jan;25(1):184-94.
Pubmed

Kleinau G, Mueller S, Jaeschke H, Grzesik P, Neumann S, Diehl A, Paschke R, Krause G
Defining structural and functional dimensions of the extracellular thyrotropin receptor region.
J Biol Chem. 2011 Jun 24;286(25):22622-31.
Pubmed

Mueller S, Kleinau G, Szkudlinski MW, Jaeschke H, Krause G, Paschke R
The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor
J Biol Chem. 2009 Jun 12;284(24):16317-24. Epub 2009 Apr 22
Pubmed

Agrawal G, Dighe RR
Critical involvement of the hinge region of the follicle-stimulating hormone receptor in the activation of the receptor.
J Biol Chem. 2009 Jan 30;284(5):2636-47. Epub 2008 Nov 24.
Pubmed

Mizutori Y, Chen CR, McLachlan SM, Rapoport B.
The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction.
Mol Endocrinol. 2008 May;22(5):1171-82
Pubmed

Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G.
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
J Biol Chem. 2008 Jun 27;283(26):18048-55
Pubmed

Bruysters M, Verhoef-Post M, Themmen AP.
Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation.
J Biol Chem. 2008 Sep 19;283(38):25821-8.
Pubmed

Bonomi M, Busnelli M, Persani L, Vassart G, Costagliola S.
Structural differences in the "hinge region" of the glycoprotein-hormone receptors: evidences from the sulfated tyrosine residues.
Mol Endocrinol. 2006 Dec;20(12):3351-63
Pubmed

Costagliola S, Panneels V, Bonomi M, Koch J, Many MC, Smits G, Vassart G
Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors
EMBO J. 2002 Feb 15;21(4):504-13
Pubmed

Russo D, Betterle C, Arturi F, Chiefari E, Girelli ME, Filetti S
A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH.
J Clin Endocrinol Metab. 2000 Nov;85(11):4238-42
Pubmed

Van Sande J, Massart C, Costagliola S, Allgeier A, Cetani F, Vassart G, Dumont JE
Specific activation of the thyrotropin receptor by trypsin
Mol Cell Endocrinol. 1996 May 31;119(2):161-8
Pubmed

Kosugi S, Ban T, Akamizu T, Kohn LD
Site-directed mutagenesis of a portion of the extracellular domain of the rat thyrotropin receptor important in autoimmune thyroid disease and nonhomologous with gonadotropin receptors. Relationship of functional and immunogenic domains
J Biol Chem. 1991 Oct 15;266(29):19413-8
Pubmed

Cysteine-box 3

Mizutori Y, Chen CR, McLachlan SM, Rapoport B.
The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction.
Mol Endocrinol. 2008 May;22(5):1171-82
Pubmed

Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G.
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
J Biol Chem. 2008 Jun 27;283(26):18048-55
Pubmed

Bruysters M, Verhoef-Post M, Themmen AP.
Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation.
J Biol Chem. 2008 Sep 19;283(38):25821-8.
Pubmed

Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R.
Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor.
J Biol Chem. 2006 Oct 20;281(42):31638-46.
Pubmed

Ho SC, Goh SS, Su Q, Khoo DH
Cysteine 390 mutation of the TSH receptor modulates its ectodomain as an inverse agonist on the serpentine domain with decrease in basal constitutive activity
Mol Cell Endocrinol. 2005 Dec 21;245(1-2):158-68
Pubmed

Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface
J Biol Chem. 2004 Dec 3;279(49):51590-600
Pubmed

Alvarez CA, Narayan P, Huang J, Puett D
Characterization of a region of the lutropin receptor extracellular domain near transmembrane helix 1 that is important in ligand-mediated signaling
Endocrinology. 1999 Apr;140(4):1775-82
Pubmed

Bernard MP, Myers RV, Moyle WR
Lutropins appear to contact two independent sites in the extracellular domain of their receptors.
Biochem J. 1998 Nov 1;335 ( Pt 3):611-7
Pubmed

Zhang R, Buczko E, Dufau ML
Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding
J Biol Chem. 1996 Mar 8;271(10):5755-60
Pubmed

Nagayama Y, Rapoport B.
Role of the carboxyl-terminal half of the extracellular domain of the human thyrotropin receptor in signal transduction.
Endocrinology. 1992 Aug;131(2):548-52.
Pubmed

Kosugi S, Ban T, Akamizu T, Kohn LD
Site-directed mutagenesis of a portion of the extracellular domain of the rat thyrotropin receptor important in autoimmune thyroid disease and nonhomologous with gonadotropin receptors. Relationship of functional and immunogenic domains
J Biol Chem. 1991 Oct 15;266(29):19413-8
Pubmed

Promiscuous Hormone Binding

De Leener A, Caltabiano G, Erkan S, Idil M, Vassart G, Pardo L, Costagliola S.
Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome.
Hum Mutat. 2008 Jan;29(1):91-8.
Pubmed

Vischer HF, Granneman JC, Koelink PJ, Marques RB, Bogerd J.
Identification of a luteinizing hormone-selective determinant in the exodomain of a follicle-stimulating hormone receptor.
Gen Comp Endocrinol. 2008 May 1;156(3):490-8
Pubmed

Royer J, Lefevre-Minisini A, Caltabiano G, Lacombe T, Malthiery Y, Savagner F, Pardo L, Rodien P.
The cloned equine thyrotropin receptor is hypersensitive to human chorionic gonadotropin; identification of three residues in the extracellular domain involved in ligand specificity.
Endocrinology. 2008 Oct;149(10):5088-96
Pubmed

De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, Costagliola S
Presence and absence of FSH receptor mutations provide some insights to spontaneous ovarian hyperstimulation syndrome physiopathology.
J Clin Endocrinol Metab. 2006 Feb;91(2):555-62
Pubmed

Bogerd J, Granneman JC, Schulz RW, Vischer HF
Fish FSH receptors bind LH: How to make the human FSH receptor to be more fishy?
Gen Comp Endocrinol. 2005 May 15;142(1-2):34-43
Pubmed

Costagliola S, Urizar E, Mendive F, Vassart G
Specificity and promiscuity of gonadotropin receptors
Reproduction. 2005 Sep;130(3):275-81
Pubmed

Montanelli L, Van Durme JJ, Smits G, Bonomi M, Rodien P, Devor EJ, Moffat-Wilson K, Pardo L, Vassart G, Costagliola S
Modulation of ligand selectivity associated with activation of the transmembrane region of the human follitropin receptor
Mol Endocrinol. 2004 Aug;18(8):2061-73
Pubmed

Montanelli L, Delbaere A, Di Carlo C, Nappi C, Smits G, Vassart G, Costagliola S
A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome
J Clin Endocrinol Metab. 2004 Apr;89(4):1255-8
Pubmed

Vasseur C, Rodien P, Beau I, Desroches A, Gerard C, de Poncheville L, Chaplot S, Savagner F, Croue A, Mathieu E, Lahlou N, Descamps P, Misrahi M
A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome
N Engl J Med. 2003 Aug 21;349(8):753-9.
Pubmed

Smits G, Govaerts C, Nubourgh I, Pardo L, Vassart G, Costagliola S
Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG
Mol Endocrinol. 2002 Apr;16(4):722-35
Pubmed

Superactive GPH analogues

Szkudlinski MW
Past, presence and future of thyroid-stimulating hormone (TSH) superactive analogs
Cancer Treat Res. 2004;122:345-56
Pubmed

Leitolf H, Tong KP, Grossmann M, Weintraub BD, Szkudlinski MW
Bioengineering of human thyrotropin superactive analogs by site-directed "lysine-scanning" mutagenesis. Cooperative effects between peripheral loops
J Biol Chem. 2000 Sep 1;275(35):27457-65
Pubmed

Grossmann M, Leitolf H, Weintraub BD, Szkudlinski MW
A rational design strategy for protein hormone superagonists
Nat Biotechnol. 1998 Sep;16(9):871-5
Pubmed

Szkudlinski MW, Teh NG, Grossmann M, Tropea JE, Weintraub BD
Engineering human glycoprotein hormone superactive analogues
Nat Biotechnol. 1996 Oct;14(10):1257-63
Pubmed

Thyrostimulin

Sellami A, Agricola HJ, Veenstra JA
Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH.
Gen Comp Endocrinol. 2011 Feb 1;170(3):582-8.
Pubmed

van Zeijl CJ, Surovtseva OV, Wiersinga WM, Fliers E, Boelen A
Acute inflammation increases pituitary and hypothalamic glycoprotein hormone subunit B5 mRNA expression in association with decreased thyrotrophin receptor mRNA expression in mice.
J Neuroendocrinol. 2011 Apr;23(4):310-9.
Pubmed

Sun SC, Hsu PJ, Wu FJ, Li SH, Lu CH, Luo CW
Thyrostimulin, but not thyroid-stimulating hormone (TSH), acts as a paracrine regulator to activate the TSH receptor in mammalian ovary.
J Biol Chem. 2010 Feb 5;285(6):3758-65
Pubmed

van Zeijl CJ, Surovtseva OV, Wiersinga WM, Boelen A, Fliers E
Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice.
Mol Cell Endocrinol. 2010 Jun 10;321(2):231-8.
Pubmed

Alvarez E, Cahoreau C, Combarnous Y.
Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules.
Reprod Biol Endocrinol. 2009 Aug 31;7:90
Pubmed

Okajima Y, Nagasaki H, Suzuki C, Suga H, Ozaki N, Arima H, Hamada Y, Civelli O, Oiso Y
Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5)
Regul Pept. 2008 Jun 5;148(1-3):62-7
Pubmed

Lantz M, Vondrichova T, Capretz A, Nilsson E, Frenander C, Bondeson AG, Ridderstrale M, Aberg M, Asman P, Groop L, Hallengren B
Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue
Thyroid. 2007 Feb;17(2):113-8
Pubmed

Okada SL, Ellsworth JL, Durnam DM, Haugen HS, Holloway JL, Kelley ML, Lewis KE, Ren H, Sheppard PO, Storey HM, Waggie KS, Wolf AC, Yao LY, Webster PJ
A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor
Mol Endocrinol. 2006 Feb;20(2):414-25
Pubmed

Nagasaki H, Wang Z, Jackson VR, Lin S, Nothacker HP, Civelli O
Differential expression of the thyrostimulin subunits, glycoprotein alpha2 and beta5 in the rat pituitary
J Mol Endocrinol. 2006 Aug;37(1):39-50
Pubmed

Sudo S, Kuwabara Y, Park JI, Hsu SY, Hsueh AJ
Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5
Endocrinology. 2005 Aug;146(8):3596-604
Pubmed

Park JI, Semyonov J, Chang CL, Hsu SY
Conservation of the heterodimeric glycoprotein hormone subunit family proteins and the LGR signaling system from nematodes to humans
Endocrine. 2005 Apr;26(3):267-76
Pubmed

Li C, Hirooka Y, Habu S, Takagi J, Gotoh M, Nogimori T
Distribution of thyrostimulin in the rat: an immunohistochemical study
Endocr Regul. 2004 Dec;38(4):131-42
Pubmed

Nakabayashi K, Matsumi H, Bhalla A, Bae J, Mosselman S, Hsu SY, Hsueh AJ
Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor
J Clin Invest. 2002 Jun;109(11):1445-52
Pubmed

Hsu SY, Nakabayashi K, Bhalla A
Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5
Mol Endocrinol. 2002 Jul;16(7):1538-51
Pubmed

Interplay Extracellular Domain/Serpentine domain (SD)

Hamidi S, Chen CR, Mizutori-Sasai Y, McLachlan SM, Rapoport B.
Relationship between Thyrotropin Receptor Hinge Region Proteolytic Posttranslational Modification and Receptor Physiological Function.
Mol Endocrinol. 2011 Jan;25(1):184-94.
Pubmed

Chen CR, McLachlan SM, Rapoport B
Evidence that the thyroid-stimulating hormone (TSH) receptor transmembrane domain influences kinetics of TSH binding to the receptor ectodomain.
J Biol Chem. 2011 Feb 25;286(8):6219-24.
Pubmed

Kleinau G, Mueller S, Jaeschke H, Grzesik P, Neumann S, Diehl A, Paschke R, Krause G
Defining structural and functional dimensions of the extracellular thyrotropin receptor region.
J Biol Chem. 2011 Jun 24;286(25):22622-31.
Pubmed

Nurwakagari P, Breit A, Hess C, Salman-Livny H, Ben-Menahem D, Gudermann T
A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation.
J Mol Endocrinol. 2007 Feb;38(1-2):259-75
Pubmed

Neumann S, Claus M, Paschke R
Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation
Eur J Endocrinol. 2005 Apr;152(4):625-34
Pubmed

Karges B, Gidenne S, Aumas C, Haddad F, Kelly PA, Milgrom E, de Roux N
Zero-length cross-linking reveals that tight interactions between the extracellular and transmembrane domains of the LH receptor persist during receptor activation
Mol Endocrinol. 2005 Aug;19(8):2086-98
Pubmed

Vlaeminck-Guillem V, Ho SC, Rodien P, Vassart G, Costagliola S
Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist
Mol Endocrinol. 2002 Apr;16(4):736-46
Pubmed

Jaquette J, Segaloff DL
Constitutive activation of the LH receptor is associated with an alteration in the conformation of the ectodomain
Mol Cell Endocrinol. 2002 Aug 30;194(1-2):211-5
Pubmed

Sangkuhl K, Schulz A, Schultz G, Schoneberg T
Structural requirements for mutational lutropin/choriogonadotropin receptor activation
J Biol Chem. 2002 Dec 6;277(49):47748-55
Pubmed

Zhang M, Tong KP, Fremont V, Chen J, Narayan P, Puett D, Weintraub BD, Szkudlinski MW
The extracellular domain suppresses constitutive activity of the transmembrane domain of the human TSH receptor: implications for hormone-receptor interaction and antagonist design
Endocrinology. 2000 Sep;141(9):3514-7
Pubmed

Zhang ML, Sugawa H, Kosugi S, Mori T
Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain
Biochem Biophys Res Commun. 1995 Jun 6;211(1):205-10
Pubmed

Transmembrane Helices 1-7 (TMHs 1-7)

Urizar E, Claeysen S, Deupi X, Govaerts C, Costagliola S, Vassart G, Pardo L
An Activation Switch in the Rhodopsin Family of G Protein-coupled Receptors: THE THYROTROPIN RECEPTOR
J Biol Chem. 2005 Apr 29;280(17):17135-41
Pubmed

Karges B, Krause G, Homoki J, Debatin KM, de Roux N, Karges W.
TSH receptor mutation V509A causes familial hyperthyroidism by release of interhelical constraints between transmembrane helices TMH3 and TMH5.
J Endocrinol. 2005 Aug;186(2):377-85
Pubmed

Fanelli F, Verhoef-Post M, Timmerman M, Zeilemaker A, Martens JW, Themmen AP
Insight into mutation-induced activation of the luteinizing hormone receptor: molecular simulations predict the functional behavior of engineered mutants at M398
Mol Endocrinol. 2004 Jun;18(6):1499-508
Pubmed

Claeysen S, Govaerts C, Lefort A, Van Sande J, Costagliola S, Pardo L, Vassart G
A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist
FEBS Lett. 2002 Apr 24;517(1-3):195-200
Pubmed

Tao YX, Mizrachi D, Segaloff DL
Chimeras of the rat and human FSH receptors (FSHRs) identify residues that permit or suppress transmembrane 6 mutation-induced constitutive activation of the FSHR via rearrangements of hydrophobic interactions between helices 6 and 7
Mol Endocrinol. 2002 Aug;16(8):1881-92
Pubmed

Angelova K, Fanelli F, Puett D
A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7
J Biol Chem. 2002 Aug 30;277(35):32202-13
Pubmed

Govaerts C, Lefort A, Costagliola S, Wodak SJ, Ballesteros JA, Van Sande J, Pardo L, Vassart G
A conserved Asn in transmembrane helix 7 is an on/off switch in the activation of the thyrotropin receptor
J Biol Chem. 2001 Jun 22;276(25):22991-9
Pubmed

Neumann S, Krause G, Chey S, Paschke R
A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation
Mol Endocrinol. 2001 Aug;15(8):1294-305
Pubmed

Angelova K, Narayan P, Simon JP, Puett D
Functional role of transmembrane helix 7 in the activation of the heptahelical lutropin receptor
Mol Endocrinol. 2000 Apr;14(4):459-71
Pubmed

Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T
Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors
J Biol Chem. 2000 Dec 1;275(48):37860-9
Pubmed

Alvarez CA, Narayan P, Huang J, Puett D
Characterization of a region of the lutropin receptor extracellular domain near transmembrane helix 1 that is important in ligand-mediated signaling
Endocrinology. 1999 Apr;140(4):1775-82
Pubmed

Abell AN, McCormick DJ, Segaloff DL
Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs
Mol Endocrinol. 1998 Dec;12(12):1857-69
Pubmed

Kosugi S, Mori T, Shenker A
An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor
Mol Pharmacol. 1998 May;53(5):894-901
Pubmed

Biebermann H, Schoneberg T, Schulz A, Krause G, Gruters A, Schultz G, Gudermann T
A conserved tyrosine residue (Y601) in transmembrane domain 5 of the human thyrotropin receptor serves as a molecular switch to determine G-protein coupling
FASEB J. 1998 Nov;12(14):1461-71
Pubmed

Min KS, Liu X, Fabritz J, Jaquette J, Abell AN, Ascoli M
Mutations that induce constitutive activation and mutations that impair signal transduction modulate the basal and/or agonist-stimulated internalization of the Lutropin/Choriogonadotropin receptor
J Biol Chem. 1998 Dec 25;273(52):34911-9
Pubmed

Kosugi S, Mori T, Shenker A
The role of Asp578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor
J Biol Chem. 1996 Dec 13;271(50):31813-7
Pubmed

Fernandez LM, Puett D
Identification of amino acid residues in transmembrane helices VI and VII of the lutropin/choriogonadotropin receptor involved in signaling
Biochemistry. 1996 Apr 2;35(13):3986-93
Pubmed

Kudo M, Osuga Y, Kobilka BK, Hsueh AJ
Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop
J Biol Chem. 1996 Sep 13;271(37):22470-8
Pubmed

Kosugi S, Shenker A, Mori T
Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor
FEBS Lett. 1994 Dec 19;356(2-3):291-4
Pubmed

Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr
A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty
Nature. 1993 Oct 14;365(6447):652-4
Pubmed

ECL1

Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G
Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor
FASEB J. 2008 Aug;22(8):2798-808
Pubmed

Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R
An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function
Endocrinology. 2006 Apr;147(4):1753-60
Pubmed

Ji I, Ji TH
Differential roles of exoloop 1 of the human follicle-stimulating hormone receptor in hormone binding and receptor activation
J Biol Chem. 1995 Jul 7;270(27):15970-3
Pubmed

Rozzell TG, Wang H, Liu X, Segaloff DL
Intracellular retention of mutant gonadotropin receptors results in loss of hormone binding activity of the follitropin receptor but not of the lutropin/choriogonadotropin receptor
Mol Endocrinol. 1995 Dec;9(12):1727-36
Pubmed

Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont J, Vassart G
Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3',5'-monophosphate and inositol phosphate-Ca2+ cascades
Mol Endocrinol. 1995 Jun;9(6):725-33
Pubmed

ECL2

Dupakuntla M, Pathak B, Roy BS, Mahale SD
Extracellular loop 2 in the FSH receptor is crucial for ligand mediated receptor activation.
Mol Cell Endocrinol. 2012 Oct 15;362(1-2):60-8.
Pubmed

Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G
Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor
FASEB J. 2008 Aug;22(8):2798-808
Pubmed

Kleinau G, Claus M, Jaeschke H, Mueller S, Neumann S, Paschke R, Krause G.
Contacts between extracellular loop two and transmembrane helix six determine basal activity of the thyroid stimulating hormone receptor.
J Biol Chem. 2007 Jan 5;282(1):518-25
Pubmed

Nishi S, Nakabayashi K, Kobilka B, Hsueh AJ
The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region: studies using chimeric human and fly receptors
J Biol Chem. 2002 Feb 8;277(6):3958-64
Pubmed

Li S, Liu X, Min L, Ascoli M
Mutations of the second extracellular loop of the human lutropin receptor emphasize the importance of receptor activation and de-emphasize the importance of receptor phosphorylation in agonist-induced internalization
J Biol Chem. 2001 Mar 16;276(11):7968-73
Pubmed

Ryu K, Lee H, Kim S, Beauchamp J, Tung CS, Isaacs NW, Ji I, Ji TH
Modulation of high affinity hormone binding. Human choriogonadotropin binding to the exodomain of the receptor is influenced by exoloop 2 of the receptor
J Biol Chem. 1998 Mar 13;273(11):6285-91
Pubmed

Couture L, Remy JJ, Rabesona H, Troalen F, Pajot-Augy E, Bozon V, Haertle T, Bidart JM, Salesse R
A defined epitope on the human choriogonadotropin alpha-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor
Eur J Biochem. 1996 Oct 15;241(2):627-32
Pubmed

ECL3

Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G
Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor
FASEB J. 2008 Aug;22(8):2798-808
Pubmed

Claus M, Jaeschke H, Kleinau G, Neumann S, Krause G, Paschke R
A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling
Endocrinology. 2005 Dec;146(12):5197-203
Pubmed

Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH
Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3
J Biol Chem. 2003 Nov 28;278(48):47868-76
Pubmed

Sohn J, Ryu K, Sievert G, Jeoung M, Ji I, Ji TH
Follicle-stimulating hormone interacts with exoloop 3 of the receptor
J Biol Chem. 2002 Dec 20;277(51):50165-75
Pubmed

Ryu K, Gilchrist RL, Tung CS, Ji I, Ji TH
High affinity hormone binding to the extracellular N-terminal exodomain of the follicle-stimulating hormone receptor is critically modulated by exoloop 3
J Biol Chem. 1998 Oct 30;273(44):28953-8
Pubmed

Fernandez LM, Puett D
Lys583 in the third extracellular loop of the lutropin/choriogonadotropin receptor is critical for signaling
J Biol Chem. 1996 Jan 12;271(2):925-30
Pubmed

Gilchrist RL, Ryu KS, Ji I, Ji TH
The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals
J Biol Chem. 1996 Aug 9;271(32):19283-7
Pubmed

Ryu KS, Gilchrist RL, Ji I, Kim SJ, Ji TH
Exoloop 3 of the luteinizing hormone/choriogonadotropin receptor. Lys583 is essential and irreplaceable for human choriogonadotropin (hCG)-dependent receptor activation but not for high affinity hCG binding
J Biol Chem. 1996 Mar 29;271(13):7301-4
Pubmed

Kosugi S, Mori T
The third exoplasmic loop of the thyrotropin receptor is partially involved in signal transduction
FEBS Lett. 1994 Jul 25;349(1):89-92
Pubmed

ICL1

Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G.
Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.
PLoS One. 2010 Mar 18;5(3):e9745
Pubmed

Kosugi S, Mori T
The first cytoplasmic loop of the thyrotropin receptor is important for phosphoinositide signaling but not for agonist-induced adenylate cyclase activation
FEBS Lett. 1994 Mar 21;341(2-3):162-6
Pubmed

Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B
Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis
J Biol Chem. 1990 Dec 5;265(34):20970-5
Pubmed

ICL2

Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G.
Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.
PLoS One. 2010 Mar 18;5(3):e9745
Pubmed

Angelova K, Fanelli F, Puett D
Contributions of intracellular loops 2 and 3 of the lutropin receptor in gs coupling
Mol Endocrinol. 2008 Jan;22(1):126-38
Pubmed

Feng X, Mueller T, Mizrachi D, Fanelli F, Segaloff DL
An intracellular loop (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and helix 6, via helix 3
Endocrinology. 2008 Apr;149(4):1705-17
Pubmed

Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA, Dias JA
Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression
Mol Cell Endocrinol. 2007 Jan 2;260-262:153-62
Pubmed

Neumann S, Krause G, Claus M, Paschke R
Structural determinants for g protein activation and selectivity in the second intracellular loop of the thyrotropin receptor
Endocrinology. 2005 Jan;146(1):477-85
Pubmed

Timossi C, Maldonado D, Vizcaino A, Lindau-Shepard B, Conn PM, Ulloa-Aguirre A
Structural determinants in the second intracellular loop of the human follicle-stimulating hormone receptor are involved in G(s) protein activation
Mol Cell Endocrinol. 2002 Mar 28;189(1-2):157-68
Pubmed

Fernandez LM, Puett D
Evidence for an important functional role of intracellular loop II of the lutropin receptor
Mol Cell Endocrinol. 1997 Apr 4;128(1-2):161-9
Pubmed

Kosugi S, Kohn LD, Akamizu T, Mori T
The middle portion in the second cytoplasmic loop of the thyrotropin receptor plays a crucial role in adenylate cyclase activation
Mol Endocrinol. 1994 Apr;8(4):498-509
Pubmed

Wang Z, Wang H, Ascoli M
Mutation of a highly conserved acidic residue present in the second intracellular loop of G-protein-coupled receptors does not impair hormone binding or signal transduction of the luteinizing hormone/chorionic gonadotropin receptor
Mol Endocrinol. 1993 Jan;7(1):85-93
Pubmed

Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B
Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis
J Biol Chem. 1990 Dec 5;265(34):20970-5
Pubmed

ICL3

Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G.
Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.
PLoS One. 2010 Mar 18;5(3):e9745
Pubmed

Angelova K, Fanelli F, Puett D
Contributions of intracellular loops 2 and 3 of the lutropin receptor in gs coupling
Mol Endocrinol. 2008 Jan;22(1):126-38
Pubmed

Feng X, Mueller T, Mizrachi D, Fanelli F, Segaloff DL
An intracellular loop (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and helix 6, via helix 3
Endocrinology. 2008 Apr;149(4):1705-17
Pubmed

Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA, Dias JA
Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression.
Mol Cell Endocrinol. 2007 Jan 2;260-262:153-62
Pubmed

Claus M, Neumann S, Kleinau G, Krause G, Paschke R.
Structural determinants for G-protein activation and specificity in the third intracellular loop of the thyroid-stimulating hormone receptor.
J Mol Med. 2006 Nov;84(11):943-54
Pubmed

Timossi C, Ortiz-Elizondo C, Pineda DB, Dias JA, Conn PM, Ulloa-Aguirre A
Functional significance of the BBXXB motif reversed present in the cytoplasmic domains of the human follicle-stimulating hormone receptor
Mol Cell Endocrinol. 2004 Aug 31;223(1-2):17-26
Pubmed

Bhaskaran RS, Min L, Krishnamurthy H, Ascoli M.
Studies with chimeras of the gonadotropin receptors reveal the importance of third intracellular loop threonines on the formation of the receptor/nonvisual arrestin complex.
Biochemistry. 2003 Dec 2;42(47):13950-9
Pubmed

Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T
Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors
J Biol Chem. 2000 Dec 1;275(48):37860-9
Pubmed

Schulz A, Schoneberg T, Paschke R, Schultz G, Gudermann T
Role of the third intracellular loop for the activation of gonadotropin receptors
Mol Endocrinol. 1999 Feb;13(2):181-90
Pubmed

Wang H, Jaquette J, Collison K, Segaloff DL
Positive charges in a putative amphiphilic helix in the carboxyl-terminal region of the third intracellular loop of the luteinizing hormone/chorionic gonadotropin receptor are not required for hormone-stimulated cAMP production but are necessary for expression of the receptor at the plasma membrane
Mol Endocrinol. 1993 Nov;7(11):1437-44
Pubmed

Kosugi S, Okajima F, Ban T, Hidaka A, Shenker A, Kohn LD
Substitutions of different regions of the third cytoplasmic loop of the thyrotropin (TSH) receptor have selective effects on constitutive, TSH-, and TSH receptor autoantibody-stimulated phosphoinositide and 3',5'-cyclic adenosine monophosphate signal generation.
Mol Endocrinol. 1993 Aug;7(8):1009-20
Pubmed

Chazenbalk GD, Nagayama Y, Wadsworth H, Russo D, Rapoport B.
Signal transduction by the human thyrotropin receptor: studies on the role of individual amino acid residues in the carboxyl terminal region of the third cytoplasmic loop.
Mol Endocrinol. 1991 Oct;5(10):1523-6
Pubmed

Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B
Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis
J Biol Chem. 1990 Dec 5;265(34):20970-5
Pubmed

Ionic influence

Munshi UM, Pogozheva ID, Menon KM
Highly conserved serine in the third transmembrane helix of the luteinizing hormone/human chorionic gonadotropin receptor regulates receptor activation
Biochemistry. 2003 Apr 8;42(13):3708-15
Pubmed

Angelova K, Puett D
Differential responses of an invariant region in the ectodomain of three glycoprotein hormone receptors to mutagenesis and assay conditions
Endocrine. 2002 Nov;19(2):147-54
Pubmed

Cetani F, Tonacchera M, Vassart G
Differential effects of NaCl concentration on the constitutive activity of the thyrotropin and the luteinizing hormone/chorionic gonadotropin receptors
FEBS Lett. 1996 Jan 2;378(1):27-31
Pubmed

Quintana J, Wang H, Ascoli M
The regulation of the binding affinity of the luteinizing hormone/choriogonadotropin receptor by sodium ions is mediated by a highly conserved aspartate located in the second transmembrane domain of G protein-coupled receptors
Mol Endocrinol. 1993 Jun;7(6):767-75
Pubmed

Dimerization

Zhang M, Guan R, Segaloff DL
Revisiting and Questioning Functional Rescue between Dimerized LH Receptor Mutants.
Mol Endocrinol. 2012 Apr;26(4):655-68.
Pubmed

Allen MD, Neumann S, Gershengorn MC
Occupancy of both sites on the thyrotropin (TSH) receptor dimer is necessary for phosphoinositide signaling.
FASEB J. 2011 Oct;25(10):3687-94.
Pubmed

Guan R, Wu X, Feng X, Zhang M, Hébert TE, Segaloff DL
Structural determinants underlying constitutive dimerization of unoccupied human follitropin receptors.
Cell Signal. 2010 Feb;22(2):247-56.
Pubmed

Rivero-Müller A, Chou YY, Ji I, Lajic S, Hanyaloglu AC, Jonas K, Rahman N, Ji TH, Huhtaniemi I
Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation.
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24
Pubmed

Latif R, Michalek K, Davies TF
Subunit interactions influence TSHR multimerization.
Mol Endocrinol. 2010 Oct;24(10):2009-18.
Pubmed

Zhang M, Feng X, Guan R, Hébert TE, Segaloff DL.
A cell surface inactive mutant of the human lutropin receptor (hLHR) attenuates signaling of wild-type or constitutively active receptors via heterodimerization.
Cell Signal. 2009 Nov;21(11):1663-71.
Pubmed

Guan R, Feng X, Wu X, Zhang M, Zhang X, Hébert TE, Segaloff DL
Bioluminescence resonance energy transfer studies reveal constitutive dimerization of the human lutropin receptor and a lack of correlation between receptor activation and the propensity for dimerization
J Biol Chem. 2009 Mar 20;284(12):7483-94. Epub 2009 Jan 15
Pubmed

Svendsen AM, Vrecl M, Knudsen L, Heding A, Wade JD, Bathgate RA, De Meyts P, Nøhr J.
Dimerization and negative cooperativity in the relaxin family peptide receptors.
Ann N Y Acad Sci. 2009 Apr;1160:54-9
Pubmed

Svendsen AM, Vrecl M, Ellis TM, Heding A, Kristensen JB, Wade JD, Bathgate RA, De Meyts P, Nøhr J.
Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2.
Endocrinology. 2008 Mar;149(3):1113-20
Pubmed

Fanelli F.
Dimerization of the lutropin receptor: Insights from computational modeling.
Mol Cell Endocrinol. 2007 Jan 2;260-262:59-64
Pubmed

Persani L, Calebiro D, Bonomi M.
Technology Insight: modern methods to monitor protein-protein interactions reveal functional TSH receptor oligomerization.
Nat Clin Pract Endocrinol Metab. 2007 Feb;3(2):180-90
Pubmed

Urizar E, Montanelli L, Loy T, Bonomi M, Swillens S, Gales C, Bouvier M, Smits G, Vassart G, Costagliola S
Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity
EMBO J.2005 Jun 1;24(11):1954-64
Pubmed

Calebiro D, de Filippis T, Lucchi S, Covino C, Panigone S, Beck-Peccoz P, Dunlap D, Persani L.
Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance.
Hum Mol Genet. 2005 Oct 15;14(20):2991-3002
Pubmed

Tao YX, Johnson NB, Segaloff DL
Constitutive and agonist-dependent self-association of the cell surface human lutropin receptor
J Biol Chem. 2004 Feb 13;279(7):5904-14
Pubmed

Ji I, Lee C, Jeoung M, Koo Y, Sievert GA, Ji TH
Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals
Mol Endocrinol. 2004 Apr;18(4):968-78
Pubmed

Kaczur V, Puskás LG, Takács M, Rácz IA, Szendroi A, Tóth S, Nagy Z, Szalai C, Balázs C, Falus A, Knudsen B, Farid NR
Evolution of the thyrotropin receptor: a G protein coupled receptor with an intrinsic capacity to dimerize.
Mol Genet Metab. 2003 Apr;78(4):275-90.
Pubmed

Latif R, Graves P, Davies TF
Ligand-dependent inhibition of oligomerization at the human thyrotropin receptor
J Biol Chem. 2002 Nov 22;277(47):45059-67
Pubmed

Ji I, Lee C, Song Y, Conn PM, Ji TH
Cis- and trans-activation of hormone receptors: the LH receptor
Mol Endocrinol. 2002 Jun;16(6):1299-308
Pubmed

Davies T, Marians R, Latif R
The TSH receptor reveals itself
J Clin Invest. 2002 Jul;110(2):161-4
Pubmed

Latif R, Graves P, Davies TF
Oligomerization of the human thyrotropin receptor: fluorescent protein-tagged hTSHR reveals post-translational complexes
J Biol Chem. 2001 Nov 30;276(48):45217-24
Pubmed

Osuga Y, Hayashi M, Kudo M, Conti M, Kobilka B, Hsueh AJ
Co-expression of defective luteinizing hormone receptor fragments partially reconstitutes ligand-induced signal generation
J Biol Chem. 1997 Oct 3;272(40):25006-12
Pubmed

Osuga Y, Kudo M, Kaipia A, Kobilka B, Hsueh AJ
Derivation of functional antagonists using N-terminal extracellular domain of gonadotropin and thyrotropin receptors
Mol Endocrinol. 1997 Oct;11(11):1659-68
Pubmed

Graves PN, Vlase H, Bobovnikova Y, Davies TF
Multimeric complex formation by the thyrotropin receptor in solubilized thyroid membranes
Endocrinology. 1996 Sep;137(9):3915-20
Pubmed

Chazenbalk GD, Kakinuma A, Jaume JC, McLachlan SM, Rapoport B
Evidence for negative cooperativity among human thyrotropin receptors overexpressed in mammalian cells.
Endocrinology. 1996 Nov;137(11):4586-91.
Pubmed

Graves PN, Vlase H, Davies TF
Folding of the recombinant human thyrotropin (TSH) receptor extracellular domain: identification of folded monomeric and tetrameric complexes that bind TSH receptor autoantibodies
Endocrinology. 1995 Feb;136(2):521-7
Pubmed

Dattatreyamurty B, Smith RA, Zhang SB, Santa-Coloma TA, Reichert LE Jr
The size of the mature membrane receptor for follicle-stimulating hormone is larger than that predicted from its cDNA
J Mol Endocrinol. 1992 Oct;9(2):115-21
Pubmed

Molecular Models

Biebermann H, Winkler F, Handke D, Teichmann A, Gerling B, Cameron F, Eichhorst J, Grüters A, Wiesner B, Kühnen P, Krude H, Kleinau G
New pathogenic thyrotropin receptor mutations decipher differentiated activity switching at a conserved helix 6 motif of family A GPCR.
J Clin Endocrinol Metab. 2012 Feb;97(2):E228-32.
Pubmed

Kleinau G, Mueller S, Jaeschke H, Grzesik P, Neumann S, Diehl A, Paschke R, Krause G
Defining structural and functional dimensions of the extracellular thyrotropin receptor region.
J Biol Chem. 2011 Jun 24;286(25):22622-31.
Pubmed

Kleinau G, Hoyer I, Kreuchwig A, Haas AK, Rutz C, Furkert J, Worth CL, Krause G, Schülein R
From molecular details of the interplay between transmembrane helices of the thyrotropin receptor to general aspects of signal transduction in family a G-protein-coupled receptors (GPCRs).
J Biol Chem. 2011 Jul 22;286(29):25859-71.
Pubmed

DeMars G, Fanelli F, Puett D
The extreme C-terminal region of Gαs differentially couples to the luteinizing hormone and beta2-adrenergic receptors.
Mol Endocrinol. 2011 Aug;25(8):1416-30.
Pubmed

Haas AK, Kleinau G, Hoyer I, Neumann S, Furkert J, Rutz C, Schülein R, Gershengorn MC, Krause G
Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor.
Cell Mol Life Sci. 2011 Jan;68(1):159-67.
Pubmed

Angelova K, Felline A, Lee M, Patel M, Puett D, Fanelli F
Conserved amino acids participate in the structure networks deputed to intramolecular communication in the lutropin receptor.
Cell Mol Life Sci. 2011 Apr;68(7):1227-39.
Pubmed

Biebermann H, Winkler F, Handke D, Grüters A, Krude H, Kleinau G
Molecular description of non-autoimmune hyperthyroidism at a neonate caused by a new thyrotropin receptor germline mutation.
Thyroid Res. 2011 Aug 3;4 Suppl 1:S8.
Pubmed

Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G
Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.
PLoS One. 2010 Mar 18;5(3):e9745.
Pubmed

Winkler F, Kleinau G, Tarnow P, Rediger A, Grohmann L, Gaetjens I, Krause G, L'Allemand D, Grüters A, Krude H, Biebermann H
A new phenotype of nongoitrous and nonautoimmune hyperthyroidism caused by a heterozygous thyrotropin receptor mutation in transmembrane helix 6.
J Clin Endocrinol Metab. 2010 Aug;95(8):3605-10.
Pubmed

Kleinau G, Krause G
Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms.
Endocr Rev. 2009 Apr;30(2):133-51.
Pubmed

Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G.
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
J Biol Chem. 2008 Jun 27;283(26):18048-55
Pubmed

Fanelli F.
Dimerization of the lutropin receptor: Insights from computational modeling.
Mol Cell Endocrinol. 2007 Jan 2;260-262:59-64
Pubmed

Puett D, Li Y, Demars G, Angelova K, Fanelli F.
A functional transmembrane complex: The luteinizing hormone receptor with bound ligand and G protein
Mol Cell Endocrinol. 2007 Jan 2;260-262:126-36.
Pubmed

Kleinau G, Claus M, Jaeschke H, Mueller S, Neumann S, Paschke R, Krause G.
Contacts between extracellular loop two and transmembrane helix six determine basal activity of the thyroid stimulating hormone receptor.
J Biol Chem. 2007 Jan 5;282(1):518-25
Pubmed

Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R
An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function
Endocrinology. 2006 Apr;147(4):1753-60
Pubmed

Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R.
Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor.
J Biol Chem. 2006 Oct 20;281(42):31638-46.
Pubmed

Claus M, Neumann S, Kleinau G, Krause G, Paschke R.
Structural determinants for G-protein activation and specificity in the third intracellular loop of the thyroid-stimulating hormone receptor.
J Mol Med. 2006 Nov;84(11):943-54
Pubmed

Urizar E, Claeysen S, Deupi X, Govaerts C, Costagliola S, Vassart G, Pardo L
An Activation Switch in the Rhodopsin Family of G Protein-coupled Receptors: THE THYROTROPIN RECEPTOR
J Biol Chem. 2005 Apr 29;280(17):17135-41
Pubmed

Zhang M, Mizrachi D, Fanelli F, Segaloff DL
The formation of a salt bridge between helices 3 and 6 is responsible for the constitutive activity and lack of hormone responsiveness of the naturally occurring L457R mutation of the human lutropin receptor.
J Biol Chem. 2005 Jul 15;280(28):26169-76
Pubmed

Karges B, Krause G, Homoki J, Debatin KM, de Roux N, Karges W.
TSH receptor mutation V509A causes familial hyperthyroidism by release of interhelical constraints between transmembrane helices TMH3 and TMH5.
J Endocrinol. 2005 Aug;186(2):377-85
Pubmed

Claus M, Jaeschke H, Kleinau G, Neumann S, Krause G, Paschke R
A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling
Endocrinology. 2005 Dec;146(12):5197-203
Pubmed

Fanelli F, Verhoef-Post M, Timmerman M, Zeilemaker A, Martens JW, Themmen AP
Insight into mutation-induced activation of the luteinizing hormone receptor: molecular simulations predict the functional behavior of engineered mutants at M398
Mol Endocrinol. 2004 Jun;18(6):1499-508
Pubmed

Montanelli L, Van Durme JJ, Smits G, Bonomi M, Rodien P, Devor EJ, Moffat-Wilson K, Pardo L, Vassart G, Costagliola S.
Modulation of ligand selectivity associated with activation of the transmembrane region of the human follitropin receptor.
Mol Endocrinol. 2004 Aug;18(8):2061-73
Pubmed

Moyle WR, Xing Y, Lin W, Cao D, Myers RV, Kerrigan JE, Bernard MP
Model of glycoprotein hormone receptor ligand binding and signaling
J Biol Chem. 2004 Oct 22;279(43):44442-59
Pubmed

Nunez Miguel R, Sanders J, Jeffreys J, Depraetere H, Evans M, Richards T, Blundell TL, Rees Smith B, Furmaniak J
Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling
Thyroid. 2004 Dec;14(12):991-1011
Pubmed

Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface
J Biol Chem. 2004 Dec 3;279(49):51590-600
Pubmed

Munshi UM, Pogozheva ID, Menon KM
Highly conserved serine in the third transmembrane helix of the luteinizing hormone/human chorionic gonadotropin receptor regulates receptor activation.
Biochemistry. 2003 Apr 8;42(13):3708-15
Pubmed

Fanelli F, Puett D
Structural aspects of luteinizing hormone receptor: information from molecular modeling and mutagenesis
Endocrine. 2002 Aug;18(3):285-93
Pubmed

Angelova K, Fanelli F, Puett D
A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7
J Biol Chem. 2002 Aug 30;277(35):32202-13
Pubmed

Neumann S, Krause G, Chey S, Paschke R
A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation
Mol Endocrinol. 2001 Aug;15(8):1294-305
Pubmed

Fanelli F
Theoretical study on mutation-induced activation of the luteinizing hormone receptor
J Mol Biol. 2000 Mar 10;296(5):1333-51
Pubmed

Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T
Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors
J Biol Chem. 2000 Dec 1;275(48):37860-9
Pubmed

Lin Z, Shenker A, Pearlstein R
A model of the lutropin/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations
Protein Eng. 1997 May;10(5):501-10
Pubmed

Small Molecules

Heitman LH, Kleinau G, Brussee J, Krause G, Ijzerman AP
Determination of different putative allosteric binding pockets at the lutropin receptor by using diverse drug-like low molecular weight ligands.
Mol Cell Endocrinol. 2012 Apr 4;351(2):326-36.
Pubmed

van Zeijl CJ, van Koppen CJ, Surovtseva OV, de Gooyer ME, Plate R, Conti P, Karstens WJ, Timmers M, Saeed P, Wiersinga WM, Miltenburg AM, Fliers E, Boelen A
Complete Inhibition of rhTSH-, Graves' Disease IgG-, and M22-Induced cAMP Production in Differentiated Orbital Fibroblasts by a Low-Molecular-Weight TSHR Antagonist.
J Clin Endocrinol Metab. 2012 Mar 14;.
Pubmed

Haas AK, Kleinau G, Hoyer I, Neumann S, Furkert J, Rutz C, Schülein R, Gershengorn MC, Krause G.
Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor.
Cell Mol Life Sci. 2011 Jan;68(1):159-67
Pubmed

Allen MD, Neumann S, Gershengorn MC
Small-molecule thyrotropin receptor agonist activates naturally occurring thyrotropin-insensitive mutants and reveals their distinct cyclic adenosine monophosphate signal persistence.
Thyroid. 2011 Aug;21(8):907-12.
Pubmed

Englund EE, Neumann S, Eliseeva E, McCoy JG, Titus S, Zheng W, Southall N, Shin P, Leister W, Thomas CJ, Inglese J, Austin CP, Gershengorn MC, Huang W
The Synthesis and Evaluation of Dihydroquinazolin-4-ones and Quinazolin-4-ones as Thyroid Stimulating Hormone Receptor Agonists.
Medchemcomm. 2011 Oct;2(10):1016-1020.
Pubmed

Newton CL, Whay AM, McArdle CA, Zhang M, van Koppen CJ, van de Lagemaat R, Segaloff DL, Millar RP
Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist.
Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7172-6.
Pubmed

Emerson CH
When will thyrotropin receptor antagonists and inverse thyrotropin receptor agonists become available for clinical use?
Thyroid. 2011 Aug;21(8):817-9.
Pubmed

Kleinau G, Haas AK, Neumann S, Worth CL, Hoyer I, Furkert J, Rutz C, Gershengorn MC, Schülein R, Krause G.
Signaling-sensitive amino acids surround the allosteric ligand binding site of the thyrotropin receptor.
FASEB J. 2010 Jul;24(7):2347-54
Pubmed

Dias JA, Bonnet B, Weaver BA, Watts J, Kluetzman K, Thomas RM, Poli SM, Mutel V, Campo B.
A negative allosteric modulator demonstrates biased antagonism of the follicle stimulating hormone receptor.
Mol Cell Endocrinol. 2010 Dec 22. [Epub ahead of print]
Pubmed

Neumann S, Huang W, Eliseeva E, Titus S, Thomas CJ, Gershengorn MC
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
Endocrinology. 2010 Jul;151(7):3454-9.
Pubmed

Titus S, Huang W, Marugan J, Southall N, Inglese J, Austin C, Zheng W, Englund E, Neumann S, Gershengorn M
Identification of Potent and Selective Thyroid Stimulating Hormone Receptor Agonists
Array. 2010;.
Pubmed

Neumann S, Huang W, Titus S, Krause G, Kleinau G, Alberobello AT, Zheng W, Southall NT, Inglese J, Austin CP, Celi FS, Gavrilova O, Thomas CJ, Raaka BM, Gershengorn MC
Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice.
Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12471-6.
Pubmed

Heitman LH, Narlawar R, de Vries H, Willemsen MN, Wolfram D, Brussee J, Ijzerman AP.
Substituted terphenyl compounds as the first class of low molecular weight allosteric inhibitors of the luteinizing hormone receptor.
J Med Chem. 2009 Apr 9;52(7):2036-42.
Pubmed

Bonger KM, van den Berg RJ, Knijnenburg AD, Heitman LH, van Koppen CJ, Timmers CM, Overkleeft HS, van der Marel GA.
Discovery of selective luteinizing hormone receptor agonists using the bivalent ligand method.
ChemMedChem. 2009 Jul;4(7):1189-95.
Pubmed

Neumann S, Raaka BM, Gershengorn MC.
Human TSH receptor ligands as pharmacological probes with potential clinical application.
Expert Rev Endocrinol Metab. 2009 Nov 1;4(6):669
Pubmed

Haugen BR.
Drugs that suppress TSH or cause central hypothyroidism.
Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):793-800
Pubmed

Arey BJ, Yanofsky SD, Claudia Pérez M, Holmes CP, Wrobel J, Gopalsamy A, Stevis PE, López FJ, Winneker RC.
Differing pharmacological activities of thiazolidinone analogs at the FSH receptor
Biochem Biophys Res Commun. 2008 Apr 11;368(3):723-8
Pubmed

Heitman L, Oosterom J, Bonger K, Timmers C, Wiegerinck P, Ijzerman AP
[3H]Org 43553, the First Low Molecular Weight Agonistic and Allosteric Radioligand for the Human Luteinizing Hormone Receptor
Mol Pharmacol. 2008 Feb;73(2):518-24
Pubmed

van Koppen CJ, Zaman GJ, Timmers CM, Kelder J, Mosselman S, van de Lagemaat R, Smit MJ, Hanssen RG
A signaling-selective, nanomolar potent allosteric low molecular weight agonist for the human luteinizing hormone receptor.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Nov;378(5):503-14.
Pubmed

Heitman LH, Ijzerman AP
G protein-coupled receptors of the hypothalamic-pituitary-gonadal axis: a case for Gnrh, LH, FSH, and GPR54 receptor ligands
Med Res Rev. 2008 Nov;28(6):975-1011
Pubmed

Neumann S, Kleinau G, Costanzi S, Moore S, Jiang JK, Raaka BM, Thomas CJ, Krause G, Gershengorn MC.
A low-molecular-weight antagonist for the human thyrotropin receptor with therapeutic potential for hyperthyroidism.
Endocrinology. 2008 Dec;149(12):5945-50
Pubmed

Arey BJ.
Allosteric modulators of glycoprotein hormone receptors: discovery and therapeutic potential.
Endocrine. 2008 Aug-Dec;34(1-3):1-10. Epub 2008 Oct 28.
Pubmed

Jorand-Lebrun C, Brondyk B, Lin J, Magar S, Murray R, Reddy A, Shroff H, Wands G, Weiser W, Xu Q, McKenna S, Brugger N
Identification, synthesis, and biological evaluation of novel pyrazoles as low molecular weight luteinizing hormone receptor agonists
Bioorg Med Chem Lett. 2007 Apr 1;17(7):2080-5
Pubmed

Jaschke H, Neumann S, Moore S, Thomas CJ, Colson AO, Costanzi S, Kleinau G, Jiang JK, Paschke R, Raaka BM, Krause G, Gershengorn MC
A low molecular weight agonist signals by binding to the transmembrane domain of thyroid-stimulating hormone receptor (TSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR)
J Biol Chem. 2006 Apr 14;281(15):9841-4
Pubmed

Yanofsky SD, Shen ES, Holden F, Whitehorn E, Aguilar B, Tate E, Holmes CP, Scheuerman R, MacLean D, Wu MM, Frail DE, Lopez FJ, Winneker R, Arey BJ, Barrett RW
Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists
J Biol Chem. 2006 May 12;281(19):13226-33
Pubmed

Wrobel J, Jetter J, Kao W, Rogers J, Di L, Chi J, Perez MC, Chen GC, Shen ES
5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists
Bioorg Med Chem. 2006 Aug 15;14(16):5729-41
Pubmed

van Straten NC, van Berkel TH, Demont DR, Karstens WJ, Merkx R, Oosterom J, Schulz J, van Someren RG, Timmers CM, van Zandvoort PM
Identification of substituted 6-amino-4-phenyltetrahydroquinoline derivatives: potent antagonists for the follicle-stimulating hormone receptor
J Med Chem. 2005 Mar 24;48(6):1697-700
Pubmed

Pelletier JC, Rogers J, Wrobel J, Perez MC, Shen ES
Preparation of highly substituted gamma-lactam follicle stimulating hormone receptor agonists
Bioorg Med Chem. 2005 Nov 1;13(21):5986-95
Pubmed

Wrobel J, Green D, Jetter J, Kao W, Rogers J, Perez MC, Hardenburg J, Deecher DC, Lopez FJ, Arey BJ, Shen ES
Synthesis of (bis)sulfonic acid, (bis)benzamides as follicle-stimulating hormone (FSH) antagonists
Bioorg Med Chem. 2002 Mar;10(3):639-569
Pubmed

Arey BJ, Deecher DC, Shen ES, Stevis PE, Meade EH Jr, Wrobel J, Frail DE, Lopez FJ
Identification and characterization of a selective, nonpeptide follicle-stimulating hormone receptor antagonist
Endocrinology. 2002 Oct;143(10):3822-9
Pubmed

LGRs4-8

Carmon KS, Lin Q, Gong X, Thomas A, Liu Q
LGR5 Interacts and Co-Internalizes with Wnt Receptors to Modulate Wnt/β-catenin Signaling.
Mol Cell Biol. 2012 Apr 2;.
Pubmed

de Lau WB, Snel B, Clevers HC
The R-spondin protein family.
Genome Biol. 2012 Mar 22;13(3):242.
Pubmed

Madka V, Rao CV
Cancer stem cell markers as potential targets for epithelial cancers.
Indian J Exp Biol. 2011 Nov;49(11):826-35.
Pubmed

Campitiello MR, De Franciscis P, Mele D, Izzo G, Sinisi A, Delrio G, Colacurci N
Endometrial LGR7 expression during menstrual cycle.
Fertil Steril. 2011 Jun 30;95(8):2511-4.
Pubmed

Leushacke M, Barker N
Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer.
Oncogene. 2011 Oct 17;.
Pubmed

Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C
LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling.
EMBO Rep. 2011 Sep 30;12(10):1055-61.
Pubmed

Carmon KS, Gong X, Lin Q, Thomas A, Liu Q
R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling.
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11452-7.
Pubmed

Koo BK, Stange DE, Sato T, Karthaus W, Farin HF, Huch M, van Es JH, Clevers H
Controlled gene expression in primary Lgr5 organoid cultures.
Nat Methods. 2011 Dec 4;9(1):81-3.
Pubmed

Hossain MA, Man BC, Zhao C, Xu Q, Du XJ, Wade JD, Samuel CS
H3 relaxin demonstrates antifibrotic properties via the RXFP1 receptor.
Biochemistry. 2011 Mar 1;50(8):1368-75.
Pubmed

de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H
Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.
Nature. 2011 Jul 4;476(7360):293-7.
Pubmed

Birchmeier W
Stem cells: Orphan receptors find a home.
Nature. 2011 Aug 17;476(7360):287-8.
Pubmed

Hirose K, Shimoda N, Kikuchi Y
Expression patterns of lgr4 and lgr6 during zebrafish development.
Gene Expr Patterns. 2011 Oct;11(7):378-83.
Pubmed

Barker N, Clevers H
Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells.
Gastroenterology. 2010 May;138(5):1681-96.
Pubmed

Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftg�rd R, Clevers H.
Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin.
Science. 2010 Mar 12;327(5971):1385-9.
Pubmed

Kato S, Siqin, Minagawa I, Aoshima T, Sagata D, Konishi H, Yogo K, Kawarasaki T, Sasada H, Tomogane H, Kohsaka T
Evidence for expression of relaxin hormone-receptor system in the boar testis.
J Endocrinol. 2010 Nov;207(2):135-49.
Pubmed

Sasaki Y, Kosaka H, Usami K, Toki H, Kawai H, Shiraishi N, Ota T, Nakamura K, Furuya A, Satoh M, Hasegawa K, Masuda K
Establishment of a novel monoclonal antibody against LGR5.
Biochem Biophys Res Commun. 2010 Apr 9;394(3):498-502.
Pubmed

Kong RC, Shilling PJ, Lobb DK, Gooley PR, Bathgate RA
Membrane receptors: structure and function of the relaxin family peptide receptors.
Mol Cell Endocrinol. 2010 May 14;320(1-2):1-15.
Pubmed

Blanpain C
Stem cells: Skin regeneration and repair.
Nature. 2010 Apr 1;464(7289):686-7.
Pubmed

Svendsen AM, Vrecl M, Knudsen L, Heding A, Wade JD, Bathgate RA, De Meyts P, Nøhr J.
Dimerization and negative cooperativity in the relaxin family peptide receptors.
Ann N Y Acad Sci. 2009 Apr;1160:54-9
Pubmed

Moore XL, Hong A, Du XJ
Alpha-adrenergic activation upregulates expression of relaxin receptor RXFP1 in cardiomyocytes.
Ann N Y Acad Sci. 2009 Apr;1160:285-6.
Pubmed

Yan Y, Scott DJ, Wilkinson TN, Ji J, Tregear GW, Bathgate RA
Identification of the N-linked glycosylation sites of the human relaxin receptor and effect of glycosylation on receptor function.
Biochemistry. 2008 Jul 1;47(26):6953-68
Pubmed

Svendsen AM, Vrecl M, Ellis TM, Heding A, Kristensen JB, Wade JD, Bathgate RA, De Meyts P, Nøhr J.
Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2.
Endocrinology. 2008 Mar;149(3):1113-20
Pubmed

Morgan BA.
A glorious revolution in stem cell biology.
Nat Genet. 2008 Nov;40(11):1269-70
Pubmed

Krusche CA, Kroll T, Beier HM, Classen-Linke I
Expression of leucine-rich repeat-containing G-protein-coupled receptors in the human cyclic endometrium
Fertil Steril. 2007 Jun;87(6):1428-37
Pubmed

Hoshii T, Takeo T, Nakagata N, Takeya M, Araki K, Yamamura K
LGR4 Regulates the Postnatal Development and Integrity of Male Reproductive Tracts in Mice
Biol Reprod. 2007 Feb;76(2):303-13
Pubmed

Van Loy T, Vandersmissen HP, Van Hiel MB, Poels J, Verlinden H, Badisco L, Vassart G, Vanden Broeck J
Comparative genomics of leucine-rich repeats containing G protein-coupled receptors and their ligands
Gen Comp Endocrinol. 2007 Jul 4
Pubmed

Scott DJ, Wilkinson TN, Zhang S, Ferraro T, Wade JD, Tregear GW, Bathgate RA
Defining the LGR8 residues involved in binding insulin-like peptide 3
Mol Endocrinol. 2007 Jul;21(7):1699-712
Pubmed

Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H.
Identification of stem cells in small intestine and colon by marker gene Lgr5.
Nature. 2007 Oct 25;449(7165):1003-7
Pubmed

Luo CW, Hsueh AJ
Genomic analyses of the evolution of LGR genes
Chang Gung Med J. 2006 Jan-Feb;29(1):2-8. Review
Pubmed

Kato S, Matsubara M, Matsuo T, Mohri Y, Kazama I, Hatano R, Umezawa A, Nishimori K
Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice
Nephron Exp Nephrol. 2006;104(2):e63-75
Pubmed

Bathgate RA, Lin F, Hanson NF, Otvos L Jr, Guidolin A, Giannakis C, Bastiras S, Layfield SL, Ferraro T, Ma S, Zhao C, Gundlach AL, Samuel CS, Tregear GW, Wade JD
Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo
Biochemistry. 2006 Jan 24;45(3):1043-53
Pubmed

Scott DJ, Layfield S, Yan Y, Sudo S, Hsueh AJ, Tregear GW, Bathgate RA
Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules.
J Biol Chem. 2006 Nov 17;281(46):34942-54
Pubmed

Liu C, Chen J, Kuei C, Sutton S, Nepomuceno D, Bonaventure P, Lovenberg TW
Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7.
Mol Pharmacol. 2005 Jan;67(1):231-40
Pubmed

Scott DJ, Tregear GW, Bathgate RA
LGR7-truncate is a splice variant of the relaxin receptor LGR7 and is a relaxin antagonist in vitro
Ann N Y Acad Sci. 2005 May;1041:22-6
Pubmed

Hsu SY, Semyonov J, Park JI, Chang CL
Evolution of the signaling system in relaxin-family peptides
Ann N Y Acad Sci. 2005 May;1041:520-9
Pubmed

Van Schoore G, Mendive F, Pochet R, Vassart G
Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse
Histochem Cell Biol. 2005 Jul;124(1):35-50
Pubmed

Park JI, Semyonov J, Chang CL, Hsu SY
Conservation of the heterodimeric glycoprotein hormone subunit family proteins and the LGR signaling system from nematodes to humans
Endocrine. 2005 Apr;26(3):267-76
Pubmed

Muda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL, Bathgate RA
Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity
Mol Hum Reprod. 2005 Aug;11(8):591-600
Pubmed

Fu P, Shen PJ, Zhao CX, Scott DJ, Samuel CS, Wade JD, Tregear GW, Bathgate RA, Gundlach AL
Detection, localization, and action of the INSL3 receptor, LGR8, in rat kidney
Ann N Y Acad Sci. 2005 May;1041:516-9
Pubmed

Lin F, Otvos L Jr, Kumagai J, Tregear GW, Bathgate RA, Wade JD
Synthetic human insulin 4 does not activate the G-protein-coupled receptors LGR7 or LGR8
J Pept Sci. 2004 May;10(5):257-64
Pubmed

Mazerbourg S, Bouley DM, Sudo S, Klein CA, Zhang JV, Kawamura K, Goodrich LV, Rayburn H, Tessier-Lavigne M, Hsueh AJ
Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality.
Mol Endocrinol. 2004 Sep;18(9):2241-54
Pubmed

Morita H, Mazerbourg S, Bouley DM, Luo CW, Kawamura K, Kuwabara Y, Baribault H, Tian H, Hsueh AJ
Neonatal lethality of LGR5 null mice is associated with ankyloglossia and gastrointestinal distension
Mol Cell Biol. 2004 Nov;24(22):9736-43
Pubmed

Herpin A, Badariotti F, Rodet F, Favrel P
Molecular characterization of a new leucine-rich repeat-containing G protein-coupled receptor from a bivalve mollusc: evolutionary implications
Biochim Biophys Acta. 2004 Nov 5;1680(3):137-44
Pubmed

Hsu SY
New insights into the evolution of the relaxin-LGR signaling system
Trends Endocrinol Metab. 2003 Sep;14(7):303-9. Review
Pubmed

Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ
Activation of orphan receptors by the hormone relaxin
Science. 2002 Jan 25;295(5555):671-4
Pubmed

Kudo M, Chen T, Nakabayashi K, Hsu SY, Hsueh AJ
The nematode leucine-rich repeat-containing, G protein-coupled receptor (LGR) protein homologous to vertebrate gonadotropin and thyrotropin receptors is constitutively active in mammalian cells
Mol Endocrinol. 2000 Feb;14(2):272-84
Pubmed

Eriksen KK, Hauser F, Schiott M, Pedersen KM, Sondergaard L, Grimmelikhuijzen CJ
Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster.
Genome Res. 2000 Jul;10(7):924-38
Pubmed

Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ
The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7.
Mol Endocrinol. 2000 Aug;14(8):1257-71
Pubmed

Nishi S, Hsu SY, Zell K, Hsueh AJ
Characterization of two fly LGR (leucine-rich repeat-containing, G protein-coupled receptor) proteins homologous to vertebrate glycoprotein hormone receptors: constitutive activation of wild-type fly LGR1 but not LGR2 in transfected mammalian cells.
Endocrinology. 2000 Nov;141(11):4081-90
Pubmed

Hsu SY, Liang SG, Hsueh AJ.
Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region.
Mol Endocrinol. 1998 Dec;12(12):1830-45.
Pubmed

Extrathyroidal TSHR

Hanon EA, Routledge K, Dardente H, Masson-Pévet M, Morgan PJ, Hazlerigg DG
Effect of photoperiod on the thyroid-stimulating hormone neuroendocrine system in the European hamster (Cricetus cricetus).
J Neuroendocrinol. 2010 Jan;22(1):51-5.
Pubmed

de Lloyd A, Bursell J, Gregory JW, Rees DA, Ludgate M
TSH receptor activation and body composition.
J Endocrinol. 2010 Jan;204(1):13-20.
Pubmed

Rubin CJ, Zody MC, Eriksson J, Meadows JR, Sherwood E, Webster MT, Jiang L, Ingman M, Sharpe T, Ka S, Hallböök F, Besnier F, Carlborg O, Bed'hom B, Tixier-Boichard M, Jensen P, Siegel P, Lindblad-Toh K, Andersson L
Whole-genome resequencing reveals loci under selection during chicken domestication.
Nature. 2010 Mar 25;464(7288):587-91.
Pubmed

Hanon EA, Lincoln GA, Fustin JM, Dardente H, Masson-Pévet M, Morgan PJ, Hazlerigg DG
Ancestral TSH mechanism signals summer in a photoperiodic mammal.
Curr Biol. 2008 Aug 5;18(15):1147-52.
Pubmed

Nakao N, Ono H, Yamamura T, Anraku T, Takagi T, Higashi K, Yasuo S, Katou Y, Kageyama S, Uno Y, Kasukawa T, Iigo M, Sharp PJ, Iwasawa A, Suzuki Y, Sugano S, Niimi T, Mizutani M, Namikawa T, Ebihara S, Ueda HR, Yoshimura T
Thyrotrophin in the pars tuberalis triggers photoperiodic response.
Nature. 2008 Mar 20;452(7185):317-22.
Pubmed

Ono H, Hoshino Y, Yasuo S, Watanabe M, Nakane Y, Murai A, Ebihara S, Korf HW, Yoshimura T
Involvement of thyrotropin in photoperiodic signal transduction in mice.
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18238-42.
Pubmed