The recent genetics of hypogonadotrophic hypogonadism - Novel insights and new questions

Clinical Endocrinology

Volumn 72, Issue 4, 2010, Pages 427-435

  Semple, Robert K ^a   Topaloglu, A Kemal ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b CUKUROVA UNIVERSITY   (Turkey)

Author keywords

[No Author keywords available]

Indexed keywords

GONADORELIN; KISSPEPTIN; NEUROKININ B;

ANOSMIA; FAMILY; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC DISORDER; GENETIC IDENTIFICATION; GONADORELIN RELEASE; HOMOZYGOSITY; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; HYPOSMIA; KALLMANN SYNDROME; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SEXUAL MATURATION;

CONSANGUINITY; EXTRACELLULAR MATRIX PROTEINS; FEMALE; FIBROBLAST GROWTH FACTOR 8; GASTROINTESTINAL HORMONES; GONADS; HUMANS; HYPOGONADISM; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; KALLMANN SYNDROME; MALE; NERVE TISSUE PROTEINS; NEUROKININ B; NEUROPEPTIDES; PHENOTYPE; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROKININ-3; RECEPTORS, PEPTIDE; SEXUAL MATURATION; TUMOR SUPPRESSOR PROTEINS;

EID: 77749255232     PISSN: 03000664     EISSN: 13652265     Source Type: Journal    
DOI: 10.1111/j.1365-2265.2009.03687.x     Document Type: Review

References (88)

1. Plant, T.M. (2008) Hypothalamic control of the pituitary-gonadal axis in higher primates: key advances over the last two decades. Journal of Neuroendocrinology, 20, 719 726.
2. Maestre de San Juan, A. (1856) Falta total de los nervios olfactorios con anosmia en un individuo en quien existia una atrofia congenita de los testiculos y miembro viril. Medico, 131, 211 221.
3. Kallmann, F.J., Schoenfeld, W.A. Barrera, S.E. (1944) The genetic aspects of primary eunuchoidism. American Journal of Mental Deficiency, XLVIII, 203 236.
4. de Morsier, G. Gauthier, G. (1963) La dysplasie olfactogenitale. Pathologie Biologie, 11, 1267 1272.
5. Amoss, M., Burgus, R., Blackwell, R. et al. (1971) Purification, amino acid composition and N-terminus of the hypothalamic luteinizing hormone releasing factor (LRF) of ovine origin. Biochemical and Biophysical Research Communications, 44, 205 210.
6. Schally, A.V., Arimura, A., Baba, Y. et al. (1971) Isolation and properties of the FSH and LH-releasing hormone. Biochemical and Biophysical Research Communications, 43, 393 399.
7. Naftolin, F., Harris, G.W. Bobrow, M. (1971) Effect of purified luteinizing hormone releasing factor on normal and hypogonadotrophic anosmic men. Nature, 232, 496 497.
8. Bick, D., Franco, B., Sherins, R.J. et al. (1992) Brief report: intragenic deletion of the KALIG-1 gene in Kallmann's syndrome. New England Journal of Medicine, 326, 1752 1755.
9. Franco, B., Guioli, S., Pragliola, A. et al. (1991) A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature, 353, 529 536.
10. Legouis, R., Hardelin, J.P., Levilliers, J. et al. (1991) The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell, 67, 423 435.
11. Schwanzel-Fukuda, M., Bick, D. Pfaff, D.W. (1989) Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Brain Research. Molecular Brain Research, 6, 311 326.
12. Albuisson, J., Pecheux, C., Carel, J.C. et al. (2005) Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Human Mutation, 25, 98 99.
13. Pedersen-White, J.R., Chorich, L.P., Bick, D.P. et al. (2008) The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Molecular Human Reproduction, 14, 367 370.
14. Oliveira, L.M., Seminara, S.B., Beranova, M. et al. (2001) The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics. Journal of Clinical Endocrinology and Metabolism, 86, 1532 1538.
15. Hardelin, J.P. Dode, C. (2008) The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sexual Development, 2, 181 193.
16. Salenave, S., Chanson, P., Bry, H. et al. (2008) Kallmann's syndrome: a comparison of the reproductive phenotypes in men carrying KAL1 and FGFR1/KAL2 mutations. Journal of Clinical Endocrinology and Metabolism, 93, 758 763.
17. Sato, N., Katsumata, N., Kagami, M. et al. (2004) Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. Journal of Clinical Endocrinology and Metabolism, 89, 1079 1088.
18. Tsai, P.S. Gill, J.C. (2006) Mechanisms of disease: insights into X-linked and autosomal-dominant Kallmann syndrome. Nature Clinical Practice. Endocrinology & Metabolism, 2, 160 171.
19. Dode, C., Levilliers, J., Dupont, J.M. et al. (2003) Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nature Genetics, 33, 463 465.
20. Pitteloud, N., Meysing, A., Quinton, R. et al. (2006) Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Molecular and Cellular Endocrinology, 254-255, 60 69.
21. Trarbach, E.B., Costa, E.M., Versiani, B. et al. (2006) Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. Journal of Clinical Endocrinology and Metabolism, 91, 4006 4012.
22. Pitteloud, N., Acierno, J.S. Jr., Meysing, A.U. et al. (2005) Reversible Kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene. Journal of Clinical Endocrinology and Metabolism, 90, 1317 1322.
23. Pitteloud, N., Acierno, J.S. Jr., Meysing, A.U. et al. (2006) Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 103, 6281 6286.
24. Xu, N., Qin, Y., Reindollar, R.H. et al. (2007) A mutation in the fibroblast growth factor receptor 1 gene causes fully penetrant normosmic isolated hypogonadotropic hypogonadism. Journal of Clinical Endocrinology and Metabolism, 92, 1155 1158.
25. Falardeau, J., Chung, W.C., Beenken, A. et al. (2008) Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. Journal of Clinical Investigation, 118, 2822 2831.
26. Cheng, M.Y., Bullock, C.M., Li, C. et al. (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature, 417, 405 410.
27. LeCouter, J., Lin, R. Ferrara, N. (2002) Endocrine gland-derived VEGF and the emerging hypothesis of organ-specific regulation of angiogenesis. Nature Medicine, 8, 913 917. (Pubitemid 35033682)
28. Lecouter, J., Lin, R. Ferrara, N. (2004) EG-VEGF: a novel mediator of endocrine-specific angiogenesis, endothelial phenotype, and function. Annals of the New York Academy of Sciences, 1014, 50 57.
29. Schweitz, H., Pacaud, P., Diochot, S. et al. (1999) MIT(1), a black mamba toxin with a new and highly potent activity on intestinal contraction. FEBS Letters, 461, 183 188.
30. Ng, K.L., Li, J.D., Cheng, M.Y. et al. (2005) Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science, 308, 1923 1927.
31. Pitteloud, N., Zhang, C., Pignatelli, D. et al. (2007) Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 104, 17447 17452.
32. Matsumoto, S., Yamazaki, C., Masumoto, K.H. et al. (2006) Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proceedings of the National Academy of Sciences of the United States of America, 103, 4140 4145.
33. Dode, C., Teixeira, L., Levilliers, J. et al. (2006) Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genetics, 2, 1649 1652.
34. Abreu, A.P., Trarbach, E.B., de Castro, M. et al. (2008) Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. Journal of Clinical Endocrinology and Metabolism, 93, 4113 4118.
35. Cole, L.W., Sidis, Y., Zhang, C. et al. (2008) Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. Journal of Clinical Endocrinology and Metabolism, 93, 3551 3559.
36. Vissers, L.E., van Ravenswaaij, C.M., Admiraal, R. et al. (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nature Genetics, 36, 955 957.
37. Kim, H.G., Kurth, I., Lan, F. et al. (2008) Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. American Journal of Human Genetics, 83, 511 519.
38. Jongmans, M.C., van Ravenswaaij-Arts, C.M., Pitteloud, N. et al. (2009) CHD7 mutations in patients initially diagnosed with Kallmann syndrome - the clinical overlap with CHARGE syndrome. Clinical Genetics, 75, 65 71.
39. Miura, K., Acierno, J.S. Jr. Seminara, S.B. (2004) Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). Journal of Human Genetics, 49, 265 268.
40. Pitteloud, N., Quinton, R., Pearce, S. et al. (2007) Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. Journal of Clinical Investigation, 117, 457 463.
41. Quinton, R., Duke, V.M., de Zoysa, P.A. et al. (1996) The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis. Journal of Clinical Endocrinology and Metabolism, 81, 3010 3017.
42. Seminara, S.B., Hayes, F.J. Crowley, W.F. Jr. (1998) Gonadotropin- releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocrine Reviews, 19, 521 539.
43. Nachtigall, L.B., Boepple, P.A., Pralong, F.P. et al. (1997) Adult-onset idiopathic hypogonadotropic hypogonadism - a treatable form of male infertility. New England Journal of Medicine, 336, 410 415.
44. Badano, J.L. Katsanis, N. (2002) Beyond Mendel: an evolving view of human genetic disease transmission. Nature Reviews. Genetics, 3, 779 789.
45. Conte, F.A., Grumbach, M.M., Kaplan, S.L. et al. (1980) Correlation of luteinizing hormone-releasing factor-induced luteinizing hormone and follicle-stimulating hormone release from infancy to 19 years with the changing pattern of gonadotropin secretion in agonadal patients: relation to the restraint of puberty. Journal of Clinical Endocrinology and Metabolism, 50, 163 168.
46. Atkinson, L.E., Bhattacharya, A.N., Monroe, S.E. et al. (1970) Effects of gonadectomy on plasma LH concentration in the rhesus monkey. Endocrinology, 87, 847 849.
47. Plant, T.M. (2001) Neurobiological bases underlying the control of the onset of puberty in the rhesus monkey: a representative higher primate. Frontiers in Neuroendocrinology, 22, 107 139.
48. Plant, T.M., Gay, V.L., Marshall, G.R. et al. (1989) Puberty in monkeys is triggered by chemical stimulation of the hypothalamus. Proceedings of the National Academy of Sciences of the United States of America, 86, 2506 2510.
49. Crowley, W.F. Jr., Pitteloud, N. Seminara, S. (2008) New genes controlling human reproduction and how you find them. Transactions of the American Clinical and Climatological Association, 119, 29 37.
50. de Roux, N., Young, J., Misrahi, M. et al. (1997) A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. New England Journal of Medicine, 337, 1597 1602.
51. Layman, L.C., Cohen, D.P., Jin, M. et al. (1998) Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nature Genetics, 18, 14 15.
52. Bouligand, J., Ghervan, C., Tello, J.A. et al. (2009) Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. New England Journal of Medicine, 360, 2742 2748.
53. Chan, Y.M., de Guillebon, A. Lang-Muritano, M., et al. (2009) GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 106, 11703 11708.
54. Beranova, M., Oliveira, L.M., Bedecarrats, G.Y. et al. (2001) Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. Journal of Clinical Endocrinology and Metabolism, 86, 1580 1588.
55. de Roux, N. (2006) GnRH receptor and GPR54 inactivation in isolated gonadotropic deficiency. Best Practice & Research. Clinical Endocrinology & Metabolism, 20, 515 528.
56. Lin, L., Conway, G.S., Hill, N.R. et al. (2006) A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia. Journal of Clinical Endocrinology and Metabolism, 91, 5117 5121.
57. Seminara, S.B., Beranova, M., Oliveira, L.M. et al. (2000) Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations. Journal of Clinical Endocrinology and Metabolism, 85, 556 562.
58. de Roux, N., Genin, E., Carel, J.C. et al. (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences of the United States of America, 100, 10972 10976.
59. Seminara, S.B., Messager, S., Chatzidaki, E.E. et al. (2003) The GPR54 gene as a regulator of puberty. New England Journal of Medicine, 349, 1614 1627.
60. Ohtaki, T., Shintani, Y., Honda, S. et al. (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 411, 613 617.
61. Gottsch, M.L., Cunningham, M.J., Smith, J.T. et al. (2004) A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology, 145, 4073 4077.
62. Matsui, H., Takatsu, Y., Kumano, S. et al. (2004) Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochemical and Biophysical Research Communications, 320, 383 388.
63. Messager, S., Chatzidaki, E.E., Ma, D. et al. (2005) Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proceedings of the National Academy of Sciences of the United States of America, 102, 1761 1766.
64. Shahab, M., Mastronardi, C., Seminara, S.B. et al. (2005) Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proceedings of the National Academy of Sciences of the United States of America, 102, 2129 2134.
65. Dhillo, W.S., Chaudhri, O.B., Patterson, M. et al. (2005) Kisspeptin-54 stimulates the hypothalamic-pituitary-gonadal axis in human males. Journal of Clinical Endocrinology and Metabolism, 90, 6609 6615.
66. Chan, Y.M., Broder-Fingert, S. Seminara, S.B. (2009) Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men. Peptides, 30, 42 48.
67. Clarkson, J. Herbison, A.E. (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology, 147, 5817 5825.
68. Castellano, J.M., Roa, J., Luque, R.M. et al. (2009) KiSS-1/kisspeptins and the metabolic control of reproduction: physiologic roles and putative physiopathological implications. Peptides, 30, 139 145.
69. Clarkson, J. Herbison, A.E. (2009) Oestrogen, kisspeptin, GPR54 and the pre-ovulatory luteinising hormone surge. Journal of Neuroendocrinology, 21, 305 311.
70. Rance, N.E. (2008) Menopause and the human hypothalamus: evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback. Peptides, 30, 111 122.
71. Lanfranco, F., Gromoll, J., von Eckardstein, S. et al. (2005) Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. European Journal of Endocrinology, 153, 845 852.
72. Semple, R.K., Achermann, J.C., Ellery, J. et al. (2005) Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. Journal of Clinical Endocrinology and Metabolism, 90, 1849 1855.
73. Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A. et al. (2007) Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. Journal of Clinical Endocrinology and Metabolism, 92, 1137 1144.
74. Cerrato, F., Shagoury, J., Kralickova, M. et al. (2006) Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism. European Journal of Endocrinology, 155 (Suppl. 1 S3 S10.
75. Pallais, J.C., Bo-Abbas, Y., Pitteloud, N. et al. (2006) Neuroendocrine, gonadal, placental, and obstetric phenotypes in patients with IHH and mutations in the G-protein coupled receptor, GPR54. Molecular and Cellular Endocrinology, 254-255, 70 77.
76. Popa, S.M., Clifton, D.K. Steiner, R.A. (2008) The role of kisspeptins and GPR54 in the neuroendocrine regulation of reproduction. Annual Review of Physiology, 70, 213 238.
77. Teles, M.G., Bianco, S.D., Brito, V.N. et al. (2008) A GPR54-activating mutation in a patient with central precocious puberty. New England Journal of Medicine, 358, 709 715.
78. Fraser, M.O. Plant, T.M. (1989) Further studies on the role of the gonads in determining the ontogeny of gonadotropin secretion in the guinea pig (Cavia porcelus). Endocrinology, 125, 906 911.
79. Goldman, B.D., Grazia, Y.R., Kamberi, I.A. et al. (1971) Serum gonadotropin concentrations in intact and castrated neonatal rats. Endocrinology, 88, 771 776.
80. Gupta, D., Rager, K., Zarzycki, J. et al. (1975) Levels of luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the circulation of sexually maturing intact male rats and after orchidectomy and experimental bilateral cryptorchidism. Journal of Endocrinology, 66, 183 193.
81. Topaloglu, A.K., Reimann, F., Guclu, M. et al. (2009) TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nature Genetics, 41, 354 358.
82. Guran, T., Tolhurst, G. Bereket, A., et al. (2009) A novel missense mutation in the first extracellular loop of the neurokinin B receptor causes hypogonadotropic hypogonadism. Journal of Clinical Endocrinology and Metabolism, 94, 3633 3639.
83. Pinto, F.M., Almeida, T.A., Hernandez, M. et al. (2004) mRNA expression of tachykinins and tachykinin receptors in different human tissues. European Journal of Pharmacology, 494, 233 239.
84. Maggi, C.A. Schwartz, T.W. (1997) The dual nature of the tachykinin NK1 receptor. Trends in Pharmacological Sciences, 18, 351 355.
85. Sandoval-Guzman, T. Rance, N.E. (2004) Central injection of senktide, an NK3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of Fos expression in the rat hypothalamus. Brain Research, 1026, 307 312.
86. Kung, T.T., Crawley, Y., Jones, H. et al. (2004) Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice. Pharmacological Research, 50, 611 615.
87. Chawla, M.K., Gutierrez, G.M., Young, W.S. 3rd. et al. (1997) Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain. Journal of Comparative Neurology, 384, 429 442.
88. Canto, P., Munguia, P., Soderlund, D. et al. (2009) Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1. Journal of Andrology, 30, 41 45.