Gonadotropin and TSH Receptors

  • Nicolas de Roux
  • Beate Doeker
  • Edwin Milgrom
Part of the Endocrine Updates book series (ENDO, volume 17)


Luteinizing hormone (LH), follicule-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) are glycoproteins synthesized by the pituitary. In females, LH stimulates androgen synthesis by ovarian thecal cells and triggers ovulation. In males, LH stimulates testosterone production by Leydig cells. In the ovary, FSH stimulates granulosa cell estrogen production from androgens synthesized in thecal cells. In males, FSH regulates Sertoli cell function in the testis. TSH stimulates thyroid hormone synthesis by thyroid follicular cells. All three are heterodimeric hormones with a common α subunit and a specific β subunit. Chorionic gonadotropin (CG) is the fourth member of this family found only in human (hCG) and equine (eCG) species where it is synthesized by the placenta. It is also a heterodimeric hormone composed of the common α subunit and a specific β subunit highly homologous to the β LH subunit.


Leydig Cell Congenital Hypothyroidism Luteinizing Hormone Receptor Thyrotropin Receptor Adenylate Cyclase Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Loosfelt H, Misrahi M, Atger M, Salesse R, Vu Hai-Luu Thi MT, Jolivet A, Guiochon-Mantel A, Sar S, Jallal B, Gamier J, Milgrom E 1989 Cloning and sequencing of porcine LH-hCG receptor cDNA: variants lacking transmembrane domain. Science 245: 525–528.PubMedCrossRefGoogle Scholar
  2. 2.
    McFarland KC, Sprengel R, Phillips HS, Kohler M, Rosemblit N, Nikolics K, Segaloff DL, Seeburg PH 1989 Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science 245: 494–499.PubMedCrossRefGoogle Scholar
  3. 3.
    Parmentier M, Libert F, Maenhaut C, Lefort A, Gerard C, Perret J, Van Sande J, Dumont JE, Vassart G 1989 Molecular cloning of the thyrotropin receptor. Science 246: 1620–1622.PubMedCrossRefGoogle Scholar
  4. 4.
    Minegishi T, Nakamura K, Takakura Y, Ibuki Y, Igarashi M, Minegish T 1991 Cloning and sequencing of human FSH receptor cDNA [published erratum appears in Biochem Biophys Res Commun 1994 Jun 15;201(2): 1057]. Biochem Biophys Res Commun 175: 1125–1130.PubMedCrossRefGoogle Scholar
  5. 5.
    Hsu SY, Liang SG, Hsueh Ai 1998 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 12: 1830–1845.PubMedCrossRefGoogle Scholar
  6. 6.
    Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ 2000 The three subfamilies of leucine-rich repeat-containing G proteincoupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7 [In Process Citation]. Mol Endocrinol 14: 1257–1271.PubMedCrossRefGoogle Scholar
  7. 7.
    Hermey G, Methner A, Schaller HC, Hermans-Borgmeyer I 1999 Identification of a novel seven-transmembrane receptor with homology to glycoprotein receptors and its expression in the adult and developing mouse. Biochem Biophys Res Commun 254: 273–279.PubMedCrossRefGoogle Scholar
  8. 8.
    Vu-Hai MT, Huet JC, Echasserieau K, Bidart JM, Floiras C, Pernollet JC, Milgrom E 2000 Posttranslational modifications of the lutropin receptor: mass spectrometric analysis. Biochemistry 39: 5509–5517.PubMedCrossRefGoogle Scholar
  9. 9.
    Hipkin RW, Sanchez-Yague J, Ascoli M 1992 Identification and characterization of a luteinizing hormone/chorionic gonadotropin ( LH/CG) receptor precursor in a human kidney cell line stably transfected with the rat luteal LH/CG receptor complementary DNA. Mol Endocrinol 6: 2210–2218.PubMedCrossRefGoogle Scholar
  10. 10.
    Misrahi M, Ghinea N, Sar S, Saunier B, Jolivet A, Loosfelt H, Cerutti M, Devauchelle G, Milgrom E 1994 Processing of the precursors of the human thyroid-stimulating hormone receptor in various eukaryotic cells (human thyrocytes, transfected L cells and baculovirus-infected insect cells). Eur J Biochem 222: 711–719.PubMedCrossRefGoogle Scholar
  11. 11.
    Vuhai-Luuthi MT, Jolivet A, Jallal B, Salesse R, Bidart JM, Houllier A, Guiochon-Mantel A, Gamier J, Milgrom E 1990 Monoclonal antibodies against luteinizing hormone receptor. Immunochemical characterization of the receptor. Endocrinology 127: 2090–2098.PubMedCrossRefGoogle Scholar
  12. 12.
    Davis D, Liu X, Segaloff DL 1995 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 9: 159–170.PubMedCrossRefGoogle Scholar
  13. 13.
    Davis DP, Rozell TG, Liu X, Segaloff DL 1997 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 11: 550–562.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhu H, Wang H, Ascoli M 1995 The lutropin/choriogonadotropin receptor is palmitoylated at intracellular cysteine residues. Mol Endocrinol 9: 141–150.PubMedCrossRefGoogle Scholar
  15. 15.
    Misrahi M, Couet J, Milgrom E 1997 Mechanisms of shedding of a soluble form of the TSH receptor. Ann Endocrinol 58: 365–369.Google Scholar
  16. 16.
    Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM 1998 The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies [published erratum appears in Endocr Rev 1999 Feb;20(1): 100]. Endocr Rev 19: 673–716.PubMedCrossRefGoogle Scholar
  17. 17.
    Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E 1992 Two-subunit structure of the human thyrotropin receptor. Proc Natl Acad Sci U S A 89: 3765–3769.PubMedCrossRefGoogle Scholar
  18. 18.
    Chazenbalk GD, Tanaka K, Nagayama Y, Kakinuma A, Jaume JC, McLachlan SM, Rapoport B 1997 Evidence that the thyrotropin receptor ectodomain contains not one, but two, cleavage sites. Endocrinology 138: 2893–2899.PubMedCrossRefGoogle Scholar
  19. 19.
    de Bernard S, Misrahi M, Huet JC, Beau I, Desroches A, Loosfelt H, Pichon C, Pernollet JC, Milgrom E 1999 Sequential cleavage and excision of a segment of the thyrotropin receptor ectodomain. J Biol Chem 274: 101–107.PubMedCrossRefGoogle Scholar
  20. 20.
    Couet J, de Bernard S, Loosfelt H, Saunier B, Milgrom E, Misrahi M 1996 Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain. Biochemistry 35: 14800–14805.PubMedCrossRefGoogle Scholar
  21. 21.
    Chazenbalk GD, McLachlan SM, Nagayama Y, Rapoport B 1996 Is receptor cleavage into two subunits necessary for thyrotropin action? Biochem Biophys Res Commun 225: 479–484.PubMedCrossRefGoogle Scholar
  22. 22.
    Couet J, Sar S, Jolivet A, Hai MT, Milgrom E, Misrahi M 1996 Shedding of human thyrotropin receptor ectodomain. Involvement of a matrix metalloprotease. J Biol Chem 271: 4545–4552.PubMedCrossRefGoogle Scholar
  23. 23.
    Gross B, Misrahi M, Sar S, Milgrom E 1991 Composite structure of the human thyrotropin receptor gene. Biochem Biophys Res Commun 177: 679–687.PubMedCrossRefGoogle Scholar
  24. 24.
    Atger M, Misrahi M, Sar S, Le Flem L, Dessen P, Milgrom E 1995 Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5’ non-coding regions. Mol Cell Endocrinol 111: 113–123.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang FP, Rannikko AS, Manna PR, Fraser HM, Huhtaniemi IT 1997 Cloning and functional expression of the luteinizing hormone receptor complementary deoxyribonucleic acid from the marmoset monkey testis: absence of sequences encoding exon 10 in other species. Endocrinology 138: 2481–2490.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang FP, Kero J, Huhtaniemi I 1998 The unique exon 10 of the human luteinizing hormone receptor is necessary for expression of the receptor protein at the plasma membrane in the human luteinizing hormone receptor, but deleterious when inserted into the human follicle-stimulating hormone receptor. Mol Cell Endocrinol 142: 165–174.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodien P, Cetani F, Costagliola S, Tonacchera M, Duprez L, Minegishi T, Govaerts C, Vassart G 1998 Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors. J Clin Endocrinol Metab 83: 4431–4434.PubMedCrossRefGoogle Scholar
  28. 28.
    Tsai-Morris CH, Buczko E, Wang W, Dufau ML 1990 Intronic nature of the rat luteinizing hormone receptor gene defines a soluble receptor subspecies with hormone binding activity. J Biol Chem 265: 19385–19388.PubMedGoogle Scholar
  29. 29.
    Graves PN, Tomer Y, Davies TF 1992 Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain. Biochem Biophys Res Commun 187: 1135–1143.PubMedCrossRefGoogle Scholar
  30. 30.
    Simoni M, Gromoll J, Nieschlag E 1997 The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 18: 739–773.PubMedCrossRefGoogle Scholar
  31. 31.
    Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE, Vassart G 1989 Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies. Biochem Biophys Res Commun 165: 1250–1255.PubMedCrossRefGoogle Scholar
  32. 32.
    VuHai-LuuThi MT, Misrahi M, Houllier A, Jolivet A, Milgrom E 1992 Variant forms of the pig lutropin/choriogonadotropin receptor. Biochemistry 31: 8377–8383.PubMedCrossRefGoogle Scholar
  33. 33.
    Murakami M, Miyashita K, Yamada M, Iriuchijima T, Mori M 1992 Characterization of human thyrotropin receptor-related peptide-like immunoreactivity in peripheral blood of Graves’ disease. Biochem Biophys Res Commun 186: 1074–1080.PubMedCrossRefGoogle Scholar
  34. 34.
    Ghinea N, Vu Hai MT, Groyer-Picard MT, Houiller A, Schoevaert D, Milgrom E 1992 Pathways of internalization of the hCG/LH receptor: immunoelectron microscopic studies in Leydig cells and transfected L-cells. J Cell Biol 118: 1347–1358.PubMedCrossRefGoogle Scholar
  35. 35.
    Baratti-Elbaz C, Ghinea N, Lahuna O, Loosfelt H, Pichon C, Milgrom E 1999 Internalization and recycling pathways of the thyrotropin receptor. Mol Endocrinol 13: 1751–1765.PubMedCrossRefGoogle Scholar
  36. 36.
    Dufau ML 1998 The luteinizing hormone receptor. Annu Rev Physiol 60: 461–496.PubMedCrossRefGoogle Scholar
  37. 37.
    Vannier B, Loosfelt H, Meduri G, Pichon C, Milgrom E 1996 Anti-human FSH receptor monoclonal antibodies: immunochemical and immunocytochemical characterization of the receptor. Biochemistry 35: 1358–1366.PubMedCrossRefGoogle Scholar
  38. 38.
    Meduri G, Vuhai-Luuthi MT, Jolivet A, Milgrom E 1992 New functional zonation in the ovary as shown by immunohistochemistry of luteinizing hormone receptor. Endocrinology 131: 366–373.PubMedCrossRefGoogle Scholar
  39. 39.
    Meduri G, Vu Hai MT, Jolivet A, Takemori S, Kominami S, Driancourt MA, Milgrom E 1996 Comparison of cellular distribution of LH receptors and steroidogenic enzymes in the porcine ovary. J Endocrinol 148: 435–446.PubMedCrossRefGoogle Scholar
  40. 40.
    Beau I, Misrahi M, Gross B, Vannier B, Loosfelt H, Hai MT, Pichon C, Milgrom E 1997 Basolateral localization and transcytosis of gonadotropin and thyrotropin receptors expressed in Madin-Darby canine kidney cells. J Biol Chem 272: 5241–5248.PubMedCrossRefGoogle Scholar
  41. 41.
    Beau I, Groyer-Picard MT, Le Bivic A, Vannier B, Loosfelt H, Milgrom E, Misrahi M 1998 The basolateral localization signal of the follicle-stimulating hormone receptor. J Biol Chem 273: 18610–18616.PubMedCrossRefGoogle Scholar
  42. 42.
    Ghinea N, Mai TV, Groyer-Picard MT, Milgrom E 1994 How protein hormones reach their target cells. Receptor-mediated transcytosis of hCG through endothelial cells. J Cell Biol 125: 87–97.PubMedCrossRefGoogle Scholar
  43. 43.
    Meduri G, Charnaux N, Loosfelt H, Jolivet A, Spyratos F, Brailly S, Milgrom E 1997 Luteinizing hormone/human chorionic gonadotropin receptors in breast cancer. Cancer Res 57: 857–864.PubMedGoogle Scholar
  44. 44.
    Venencie PY, Meduri G, Pissard S, Jolivet A, Loosfelt H, Milgrom E, Misrahi M 1999 Luteinizing hormone/human chorionic gonadotrophin receptors in various epidermal structures. Br J Dermatol 141: 438–446.PubMedCrossRefGoogle Scholar
  45. 45.
    Wasowicz G, Derecka K, Stepien A, Pelliniemi L, Doboszynska T, Gawronska B, Ziecik AJ 1999 Evidence for the presence of luteinizing hormone-chorionic gonadotrophin receptors in the pig umbilical cord. J Reprod Fertil 117: 1–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Kajava AV, Vassart G, Wodak SJ 1995 Modeling of the three-dimensional structure of proteins with the typical leucine-rich repeats. Structure 3: 867–877.PubMedCrossRefGoogle Scholar
  47. 47.
    Zhang R, Buczko E, Dufau ML 1996 Requirement of cysteine residues in exons 1–6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding. J Biol Chem 271: 5755–5760.PubMedCrossRefGoogle Scholar
  48. 48.
    Kosugi S, Ban T, Akamizu T, Kohn LD 1992 Role of cysteine residues in the extracellular domain and exoplasmic loops of the transmembrane domain of the TSH receptor: effect of mutation to serine on TSH receptor activity and response to thyroid stimulating autoantibodies. Biochem Biophys Res Commun 189: 1754–1762.PubMedCrossRefGoogle Scholar
  49. 49.
    Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G 1996 The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Natl Acad Sci U S A 93: 116–120.PubMedCrossRefGoogle Scholar
  50. 50.
    Herrlich A, Kuhn B, Grosse R, Schmid A, Schultz G, Gudermann T 1996 Involvement of Gs and Gi proteins in dual coupling of the luteinizing hormone receptor to adenylyl cyclase and phospholipase C. J Biol Chem 271: 16764–16772.PubMedCrossRefGoogle Scholar
  51. 51.
    Kopp P, Muirhead S, Jourdain N, Gu WX, Jameson JL, Rodd C 1997 Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation in the extracellular domain of the thyrotropin receptor. J Clin Invest 100: 1634–1639.PubMedCrossRefGoogle Scholar
  52. 52.
    Nakabayashi K, Kudo M, Kobilka B, Hsueh AJ 2000 Activation of the luteinizing hormone receptor following substitution of ser-277 with selective hydrophobic residues in the ectodomain hinge region. J Biol Chem 275: 30264–30271.PubMedCrossRefGoogle Scholar
  53. 53.
    Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont J, Vassart G 1995 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 9: 725–733.PubMedCrossRefGoogle Scholar
  54. 54.
    De Roux N, Misrahi M, Brauner R, Houang M, Carel JC, Granier M, Le Bouc Y, Ghinea N, Boumedienne A, Toublanc JE, Milgrom E 1996 Four families with loss of function mutations of the thyrotropin receptor. J Clin Endocrinol Metab 81: 4229–4235.PubMedCrossRefGoogle Scholar
  55. 55.
    Alvarez CA, Narayan P, Huang J, Puett D 1999 Characterization of a region of the lutropin receptor extracellular domain near transmembrane helix 1 that is important in ligand-mediated signaling. Endocrinology 140: 1775–1782.PubMedCrossRefGoogle Scholar
  56. 56.
    Duprez L, Parma J, Van Sande J, Rodien P, Sabine C, Abramowicz M, Dumont JE, Vassart G 1999 Pathology of the TSH receptor. J Pediatr Endocrinol Metab 12 Suppl 1: 295–302.Google Scholar
  57. 57.
    Ji TH, Ryu KS, Gilchrist R, Ji I 1997 Interaction, signal generation, signal divergence, and signal transduction of LH/CG and the receptor. Recent Prog Horm Res 52: 431–453.PubMedGoogle Scholar
  58. 58.
    Zhang M, Tong KP, Fremont V, Chen J, Narayan P, Puett D, Weintraub BD, Szkudlinski MW 2000 The extracellular domain suppresses constitutive activity of the transmembrane domain of the human TSH receptor: implications for hormone-receptor interaction and antagonist design. Endocrinology 141: 3514–3517.PubMedCrossRefGoogle Scholar
  59. 59.
    Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G 1993 Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365: 649–651.PubMedCrossRefGoogle Scholar
  60. 60.
    Duprez L, Parma J, Van Sande J, Allgeier A, Leelere J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J, et al. 1994 Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet 7: 396–401.PubMedCrossRefGoogle Scholar
  61. 61.
    de Roux N, Polak M, Couet J, Leger J, Czernichow P, Milgrom E, Misrahi M 1996 A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab 81: 2023–2026.PubMedCrossRefGoogle Scholar
  62. 62.
    Themmen APN, Huhtaniemi IT 2000 Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 21: 551–583.PubMedCrossRefGoogle Scholar
  63. 63.
    Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A 1999 Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med 341: 1731–1736.PubMedCrossRefGoogle Scholar
  64. 64.
    Sunthornthepvarakul T, Gottschalk M-E, Hayashi Y, Refetoff S 1995 Resistance to thyrotropin caused by mutations in the thyrotropin receptor gene. N Engl J Med 332: 155–160.CrossRefGoogle Scholar
  65. 65.
    Clifton-Bligh RJ, Gregory JW, Ludgate M, John R, Persani L, Asteria C, Beck-Peccoz P, Chatterjee VK 1997 Two novel mutations in the thyrotropin ( TSH) receptor gene in a child with resistance to TSH. J Clin Endocrinol Metab 82: 1094–1100.PubMedCrossRefGoogle Scholar
  66. 66.
    Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C 1997 Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest 99: 3018–3024.PubMedCrossRefGoogle Scholar
  67. 67.
    Tiosano D, Pannain S, Vassart G, Parma J, Gershoni-Baruch R, Mandel H, Lotan R, Zaharan Y, Pery M, Weiss RE, Refetoff S, Hochberg Z 1999 The hypothyroidism in an inbred kindred with congenital thyroid hormone and glucocorticoid deficiency is due to a mutation producing a truncated thyrotropin receptor. Thyroid 9: 887–894.PubMedCrossRefGoogle Scholar
  68. 68.
    Tonacchera M, Agretti P, Pinchera A, Rosellini V, Perri A, Collecchi P, Vitti P, Chiovato L 2000 Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene. J Clin Endocrinol Metab 85: 1001–1008.PubMedCrossRefGoogle Scholar
  69. 69.
    Gagne N, Parma J, Deal C, Vassart G, Van Vliet G 1998 Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities? J Clin Endocrinol Metab 83: 1771–1775.PubMedCrossRefGoogle Scholar
  70. 70.
    Biebermann H, Schoneberg T, Krude H, Schultz G, Gudermann T, Gruters A 1997 Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism. J Clin Endocrinol Metab 82: 3471–3480.PubMedCrossRefGoogle Scholar
  71. 70a.
    Stanbury JB, Rocmans P, Buhler UK, Ochi Y 1968 Congenital hypothyroidism with impaired thyroid response to thyrotropin. N Engl J Med 279: 1132–1136PubMedCrossRefGoogle Scholar
  72. 71.
    Codaccioni JL, Carayon P, Michel-Bechet M, Foucault F, Lefort G, Pierron H 1980 Congenital hypothyroidism associated with thyrotropin unresponsiveness and thyroid cell membrane alterations. J Clin Endocrinol Metab 50: 932–937.PubMedCrossRefGoogle Scholar
  73. 72.
    Xie J, Pannain S, Pohlenz J, Weiss RE, Moltz K, Morlot M, Asteria C, Persani L, Beck-Peccoz P, Parma J, Vassart G, Refetoff S 1997 Resistance to thyrotropin ( TSH) in three families is not associated with mutations in the TSH receptor or TSH [see comments]. J Clin Endocrinol Metab 82: 3933–3940.PubMedCrossRefGoogle Scholar
  74. 73.
    Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, Milgrom E, Ropers HH, Mariman E, et al. 1995 Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet 9: 160–164.PubMedCrossRefGoogle Scholar
  75. 74.
    Misrahi M, Meduri G, Pissard S, Bouvattier C, Beau I, Loosfelt H, Jolivet A, Rappaport R, Milgrom E, Bougneres P 1997 Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor. J Clin Endocrinol Metab 82: 2159–2165.PubMedCrossRefGoogle Scholar
  76. 75.
    Gromoll J, Eiholzer U, Nieschlag E, Simoni M 2000 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 85: 2281–2286.PubMedCrossRefGoogle Scholar
  77. 76.
    Laue LL, Wu SM, Kudo M, Bourdony CJ, Cutler GB, Hsueh AJ, Chan WY 1996 Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia. Mol Endocrinol 10: 987–997.PubMedCrossRefGoogle Scholar
  78. 77.
    Arnhold IJ, Latronico AC, Batista MC, Mendonca BB 1999 Menstrual disorders and infertility caused by inactivating mutations of the luteinizing hormone receptor gene. Fertil Steril 71: 597–601.PubMedCrossRefGoogle Scholar
  79. 78.
    Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, et al. 1995 Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82: 959–968.PubMedCrossRefGoogle Scholar
  80. 79.
    Beau I, Touraine P, Meduri G, Gougeon A, Desroches A, Matuchansky C, Milgrom E, Kuttenn F, Misrahi M 1998 A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest 102: 1352–1359.PubMedCrossRefGoogle Scholar
  81. 80.
    Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Panel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M 1999 New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol 13: 1844–1854.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Nicolas de Roux
    • 1
  • Beate Doeker
    • 1
  • Edwin Milgrom
    • 1
  1. 1.INSERM Unit135, Laboratoire d’Hormonologie et de Biologie MoleculaireHôpital BicêtreLe Kremlin BicêtreFrance

Personalised recommendations