GnRH receptor mutations in isolated gonadotropic deficiency

Molecular and Cellular Endocrinology

Volumn 346, Issue 1-2, 2011, Pages 21-28

  Chevrier, L ^a,b   Guimiot, F ^a,b   de Roux, N ^a,b  

^a HÔPITAL ROBERT DEBRÉ   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

GnRH receptor mutations; Hypothalamo pituitary axis; Intracellular trafficking; Variable phenotype

Indexed keywords

G PROTEIN COUPLED RECEPTOR; GONADORELIN; GONADORELIN RECEPTOR;

FETUS DEVELOPMENT; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GONADOTROPIN DEFICIENCY; HORMONAL REGULATION; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; HYPOTHALAMUS HYPOPHYSIS SYSTEM; LOSS OF FUNCTION MUTATION; MOLECULAR PATHOLOGY; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

ANIMALS; DEVELOPMENTAL BIOLOGY; GONADOTROPIN-RELEASING HORMONE; HUMANS; HYPOGONADISM; MUTATION; PHENOTYPE; RECEPTORS, LHRH;

EID: 80053383751     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.04.018     Document Type: Review

References (67)

1. Allen L.F., Lefkowitz R.J., Caron M.G., Cotecchia S. G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity. Proc. Natl. Acad. Sci. USA 1991, 88:11354-11358.
2. Antelli A., Baldazzi L., Balsamo A., Pirazzoli P., Nicoletti A., Gennari M., Cicognani A. Two novel GnRHR gene mutations in two siblings with hypogonadotropic hypogonadism. Eur. J. Endocrinol. 2006, 155:201-205.
3. Bedecarrats G.Y., Linher K.D., Janovick J.A., Beranova M., Kada F., Seminara S.B., Michael Conn P., Kaiser U.B. Four naturally occurring mutations in the human GnRH receptor affect ligand binding and receptor function. Mol. Cell. Endocrinol. 2003, 205:51-64.
4. Bedecarrats G.Y., Linher K.D., Kaiser U.B. Two common naturally occurring mutations in the human gonadotropin-releasing hormone (GnRH) receptor have differential effects on gonadotropin gene expression and on GnRH-mediated signal transduction. J. Clin. Endocrinol. Metab. 2003, 88:834-843.
5. Beranova M., Oliveira L.M., Bedecarrats G.Y., Schipani E., Vallejo M., Ammini A.C., Quintos J.B., Hall J.E., Martin K.A., Hayes F.J., Pitteloud N., Kaiser U.B., Crowley W.F., Seminara S.B. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2001, 86:1580-1588.
6. Bouligand J., Ghervan C., Tello J.A., Brailly-Tabard S., Salenave S., Chanson P., Lombes M., Millar R.P., Guiochon-Mantel A., Young J. Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. N. Engl. J. Med. 2009, 360:2742-2748.
7. Brothers S.P., Cornea A., Janovick J.A., Conn P.M. Human loss-of-function gonadotropin-releasing hormone receptor mutants retain wild-type receptors in the endoplasmic reticulum: molecular basis of the dominant-negative effect. Mol. Endocrinol. 2004, 18:1787-1797.
8. Buchberger A., Bukau B., Sommer T. Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol. Cell 2010, 40:238-252.
9. Cariboni A., Maggi R. Kallmann's syndrome, a neuronal migration defect. Cell. Mol. Life Sci. 2006, 63:2512-2526.
10. Caron P., Chauvin S., Christin-Maitre S., Bennet A., Lahlou N., Counis R., Bouchard P., Kottler M.L. Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration. J. Clin. Endocrinol. Metab. 1999, 84:990-996.
11. Chan Y.M., de Guillebon A., Lang-Muritano M., Plummer L., Cerrato F., Tsiaras S., Gaspert A., Lavoie H.B., Wu C.H., Crowley W.F., Amory J.K., Pitteloud N., Seminara S.B. GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proc. Natl. Acad. Sci. USA 2009, 106:11703-11708.
12. Ciofi P. Phenotypical segregation among female rat hypothalamic gonadotropin-releasing hormone neurons as revealed by the sexually dimorphic coexpression of cholecystokinin and neurotensin. Neuroscience 2000, 99:133-147.
13. Costa E.M., Bedecarrats G.Y., Mendonca B.B., Arnhold I.J., Kaiser U.B., Latronico A.C. Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction. J. Clin. Endocrinol. Metab. 2001, 86:2680-2686.
14. d'Anglemont de Tassigny X., Colledge W.H. The role of kisspeptin signaling in reproduction. Physiology (Bethesda) 2010, 25:207-217.
15. Davidson J.S., Flanagan C.A., Zhou W., Becker I.I., Elario R., Emeran W., Sealfon S.C., Millar R.P. Identification of N-glycosylation sites in the gonadotropin-releasing hormone receptor: role in receptor expression but not ligand binding. Mol. Cell. Endocrinol. 1995, 107:241-245.
16. Davidson J.S., Flanagan C.A., Davies P.D., Hapgood J., Myburgh D., Elario R., Millar R.P., Forrest-Owen W., McArdle C.A. Incorporation of an additional glycosylation site enhances expression of functional human gonadotropin-releasing hormone receptor. Endocrine 1996, 4:207-212.
17. de Roux N., Misrahi M., Brauner R., Houang M., Carel J.C., Granier M., Le Bouc Y., Ghinea N., Boumedienne A., Toublanc J.E., Milgrom E. Four families with loss of function mutations of the thyrotropin receptor. J. Clin. Endocrinol. Metab. 1996, 81:4229-4235.
18. de Roux N., Young J., Misrahi M., Genet R., Chanson P., Schaison G., Milgrom E. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N. Engl. J. Med. 1997, 337:1597-1602.
19. de Roux N., Young J., Brailly-Tabard S., Misrahi M., Milgrom E., Schaison G. The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred. J. Clin. Endocrinol. Metab. 1999, 84:567-572.
20. Dewailly D., Boucher A., Decanter C., Lagarde J.P., Counis R., Kottler M.L. Spontaneous pregnancy in a patient who was homozygous for the Q106R mutation in the gonadotropin-releasing hormone receptor gene. Fertil. Steril. 2002, 77:1288-1291.
21. Dobson C.M. The structural basis of protein folding and its links with human disease. Philos. Trans. R. Soc. Lond. B: Biol. Sci. 2001, 356:133-145.
22. Dryja T.P., McGee T.L., Reichel E., Hahn L.B., Cowley G.S., Yandell D.W., Sandberg M.A., Berson E.L. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 1990, 343:364-366.
23. Finch A.R., Sedgley K.R., Caunt C.J., McArdle C.A. Plasma membrane expression of GnRH receptors: regulation by antagonists in breast, prostate, and gonadotrope cell lines. J. Endocrinol. 2008, 196:353-367.
24. Finch A.R., Caunt C.J., Armstrong S.P., McArdle C.A. Plasma membrane expression of gonadotropin-releasing hormone receptors: regulation by peptide and nonpeptide antagonists. Mol. Endocrinol. 2010, 24:423-435.
25. Forest M.G., De Peretti E., Bertrand J. Hypothalamic-pituitary-gonadal relationships in man from birth to puberty. Clin. Endocrinol. (Oxf.) 1976, 5:551-569.
26. Gianetti E., Tusset C., Noel S.D., Au M.G., Dwyer A.A., Hughes V.A., Abreu A.P., Carroll J., Trarbach E., Silveira L.F., Costa E.M., de Mendonca B.B., de Castro M., Lofrano A., Hall J.E., Bolu E., Ozata M., Quinton R., Amory J.K., Stewart S.E., Arlt W., Cole T.R., Crowley W.F., Kaiser U.B., Latronico A.C., Seminara S.B. TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood. J. Clin. Endocrinol. Metab. 2010, 95:2857-2867.
27. Grumbach M.M. The neuroendocrinology of human puberty revisited. Horm. Res. 2002, 57(Suppl. 2):2-14.
28. Janovick J.A., Maya-Nunez G., Conn P.M. Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target. J. Clin. Endocrinol. Metab. 2002, 87:3255-3262.
29. Kaiser U.B., Dushkin H., Altherr M.R., Beier D.R., Chin W.W. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5. Genomics 1994, 20:506-508.
30. Kakar S.S., Musgrove L.C., Devor D.C., Sellers J.C., Neill J.D. Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem. Biophys. Res. Commun. 1992, 189:289-295.
31. Karges B., Karges W., Mine M., Ludwig L., Kuhne R., Milgrom E., de Roux N. Mutation Ala(171)Thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2003, 88:1873-1879.
32. Kaushal S., Khorana H.G. Structure and function in rhodopsin: 7. Point mutations associated with autosomal dominant retinitis pigmentosa. Biochemistry 1994, 33:6121-6128.
33. Kopito R.R., Ron D. Conformational disease. Nat. Cell Biol. 2000, 2:E207-E209.
34. Kottler M.L., Chauvin S., Lahlou N., Harris C.E., Johnston C.J., Lagarde J.P., Bouchard P., Farid N.R., Counis R. A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect. J. Clin. Endocrinol. Metab. 2000, 85:3002-3008.
35. Layman L.C. The molecular basis of human hypogonadotropic hypogonadism. Mol. Genet. Metab. 1999, 68:191-199.
36. Layman L.C., Cohen D.P., Jin M., Xie J., Li Z., Reindollar R.H., Bolbolan S., Bick D.P., Sherins R.R., Duck L.W., Musgrove L.C., Sellers J.C., Neill J.D. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat. Genet. 1998, 18:14-15.
37. Layman L.C., McDonough P.G., Cohen D.P., Maddox M., Tho S.P., Reindollar R.H. Familial gonadotropin-releasing hormone resistance and hypogonadotropic hypogonadism in a family with multiple affected individuals. Fertil. Steril. 2001, 75:1148-1155.
38. Layman L.C., Cohen D.P., Xie J., Smith G.D. Clinical phenotype and infertility treatment in a male with hypogonadotropic hypogonadism due to mutations Ala129Asp/Arg262Gln of the gonadotropin-releasing hormone receptor. Fertil. Steril. 2002, 78:1317-1320.
39. Leanos-Miranda A., Janovick J.A., Conn P.M. Receptor-misrouting: an unexpectedly prevalent and rescuable etiology in gonadotropin-releasing hormone receptor-mediated hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2002, 87:4825-4828.
40. Leanos-Miranda A., Ulloa-Aguirre A., Janovick J.A., Conn P.M. In vitro coexpression and pharmacological rescue of mutant gonadotropin-releasing hormone receptors causing hypogonadotropic hypogonadism in humans expressing compound heterozygous alleles. J. Clin. Endocrinol. Metab. 2005, 90:3001-3008.
41. Lin L., Conway G.S., Hill N.R., Dattani M.T., Hindmarsh P.C., Achermann J.C. A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia. J. Clin. Endocrinol. Metab. 2006, 91:5117-5121.
42. Liu F., Austin D.A., Mellon P.L., Olefsky J.M., Webster N.J. GnRH activates ERK1/2 leading to the induction of c-fos and LHbeta protein expression in LbetaT2 cells. Mol. Endocrinol. 2002, 16:419-434.
43. Mason A.J., Hayflick J.S., Zoeller R.T., Young W.S., Phillips H.S., Nikolics K., Seeburg P.H. A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science 1986, 234:1366-1371.
44. Maya-Nunez G., Janovick J.A., Ulloa-Aguirre A., Soderlund D., Conn P.M., Mendez J.P. Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site. J. Clin. Endocrinol. Metab. 2002, 87:2144-2149.
45. Meysing A.U., Kanasaki H., Bedecarrats G.Y., Acierno J.S., Conn P.M., Martin K.A., Seminara S.B., Hall J.E., Crowley W.F., Kaiser U.B. GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone. J. Clin. Endocrinol. Metab. 2004, 89:3189-3198.
46. Millar R.P., Lu Z.L., Pawson A.J., Flanagan C.A., Morgan K., Maudsley S.R. Gonadotropin-releasing hormone receptors. Endocr. Rev. 2004, 25:235-275.
47. Morello J.P., Salahpour A., Petaja-Repo U.E., Laperriere A., Lonergan M., Arthus M.F., Nabi I.R., Bichet D.G., Bouvier M. Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry 2001, 40:6766-6775.
48. Naor Z. Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor. Front. Neuroendocrinol. 2009, 30:10-29.
49. Pawson A.J., Faccenda E., Maudsley S., Lu Z.L., Naor Z., Millar R.P. Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology 2008, 149:1415-1422.
50. Pitteloud N., Boepple P.A., DeCruz S., Valkenburgh S.B., Crowley W.F., Hayes F.J. The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. J. Clin. Endocrinol. Metab. 2001, 86:2470-2475.
51. Plant T.M. Hypothalamic control of the pituitary-gonadal axis in higher primates: key advances over the last two decades. J. Neuroendocrinol. 2008, 20:719-726.
52. Pralong F.P., Gomez F., Castillo E., Cotecchia S., Abuin L., Aubert M.L., Portmann L., Gaillard R.C. Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor. J. Clin. Endocrinol. Metab. 1999, 84:3811-3816.
53. Rivero-Muller A., Chou Y.Y., Ji I., Lajic S., Hanyaloglu A.C., Jonas K., Rahman N., Ji T.H., Huhtaniemi I. Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation. Proc. Natl. Acad. Sci. USA 2010, 107:2319-2324.
54. Schwanzel-Fukuda M., Crossin K.L., Pfaff D.W., Bouloux P.M., Hardelin J.P., Petit C. Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos. J. Comp. Neurol. 1996, 366:547-557.
55. Sedlmeyer I.L., Pearce C.L., Trueman J.A., Butler J.L., Bersaglieri T., Read A.P., Clayton P.E., Kolonel L.N., Henderson B.E., Hirschhorn J.N., Palmert M.R. Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing. J. Clin. Endocrinol. Metab. 2005, 90:1091-1099.
56. Seminara S.B., Hayes F.J., Crowley W.F. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr. Rev. 1998, 19:521-539.
57. Silveira L.F., Stewart P.M., Thomas M., Clark D.A., Bouloux P.M., MacColl G.S. Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR "knockout". J. Clin. Endocrinol. Metab. 2002, 87:2973-2977.
58. Soderlund D., Canto P., de la Chesnaye E., Ulloa-Aguirre A., Mendez J.P. A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene. Clin. Endocrinol. (Oxf.) 2001, 54:493-498.
59. Sykiotis G.P., Plummer L., Hughes V.A., Au M., Durrani S., Nayak-Young S., Dwyer A.A., Quinton R., Hall J.E., Gusella J.F., Seminara S.B., Crowley W.F., Pitteloud N. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc. Natl. Acad. Sci. USA 2010, 107:15140-15144.
60. Topaloglu A.K., Lu Z.L., Farooqi I.S., Mungan N.O., Yuksel B., O'Rahilly S., Millar R.P. Molecular genetic analysis of normosmic hypogonadotropic hypogonadism in a Turkish population: identification and detailed functional characterization of a novel mutation in the gonadotropin-releasing hormone receptor gene. Neuroendocrinology 2006, 84:301-308.
61. Vagenakis G.A., Sgourou A., Papachatzopoulou A., Kourounis G., Papavassiliou A.G., Georgopoulos N.A. The gonadotropin-releasing hormone (GnRH)-1 gene, the GnRH receptor gene, and their promoters in patients with idiopathic hypogonadotropic hypogonadism with or without resistance to GnRH action. Fertil. Steril. 2005, 84:1762-1765.
62. Waldhauser F., Weissenbacher G., Frisch H., Pollak A. Pulsatile secretion of gonadotropins in early infancy. Eur. J. Pediatr. 1981, 137:71-74.
63. Weiss J., Adams E., Whitcomb R.W., Crowley W.F., Jameson J.L. Normal sequence of the gonadotropin-releasing hormone gene in patients with idiopathic hypogonadotropic hypogonadism. Biol. Reprod. 1991, 45:743-747.
64. Winter J.S., Faiman C., Reyes F.I. Sex steroid production by the human fetus: its role in morphogenesis and control by gonadotropins. Birth Defects Orig. Art. Ser. 1977, 13:41-58.
65. Wray S. From nose to brain: development of gonadotrophin-releasing hormone-1 neurones. J. Neuroendocrinol. 2010, 22:743-753.
66. Wu S., Wilson M.D., Busby E.R., Isaac E.R., Sherwood N.M. Disruption of the single copy gonadotropin-releasing hormone receptor in mice by gene trap: severe reduction of reproductive organs and functions in developing and adult mice. Endocrinology 2010, 151:1142-1152.
67. Young J., Bouligand J., Francou B., Raffin-Sanson M.L., Gaillez S., Jeanpierre M., Grynberg M., Kamenicky P., Chanson P., Brailly-Tabard S., Guiochon-Mantel A. TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J. Clin. Endocrinol. Metab. 2010, 95:2287-2295.