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Idiopathic Hypogonadotropic Hypogonadism— An Update on the Aetiopathogenesis, Management of IHH in Both Males and Females—An Exhaustive Review

DOI: 10.4236/asm.2016.64007, PP. 50-78

Keywords: Idiopathic Hypogonadotropic Hypogonadism, Kallmannsyndrome, Anosmia, Hyposmia, Normosmia, Gene Mutations

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Abstract:

Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future research should be directed based on animal studies. Results: Besides the 9 known mutations widely quoted for KS namely KAL1, Fibroblast growth factor 8 (FGF8), fibroblast growth factor receptor 1 (FGFR1), prokineticin 2 (PROK2), PROK receptor 2 (PROKR2), WDR11, heparin sulfate-6-O-Transferase (HS6T1), chromodomain helicase DNA binding protein 7 (CHD7) and semaphorin 3A (SEMA 3A), additional mutations in “FGF8 synexpression” group e.g., FGF 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A. Although traditionally division has been based on anosmic/normosnic criteria, further genes found to cause so called nIHH like Gonadotropin releasing hormone receptor (GNRHR). KISS1, TAC3, TACR3 have also been found to be associated with hyposmia on detailed testing on UPSIT and MRI for olfactory structures revealed absent OB. Further detailed examination of transcription factor genes have revealed involvement of HESX1, TSHZ1, AXL, SOX10 with a strong overlap of in transcription factors in development of septooptic dysplasia (SOD), combined pituitary hormone deficiency (CHPD) and KS. Treatment with rFSH/-hCG gives almost similar results to pulsatile GnRH therapy and should be based on cost factor, availability and in occasional cases specific treatment like kisspeptin therapy. Conclusions: Contrary to the traditional thinking, one shoud reconsider classifying cases of IHH simply on basis of anosmia/normosmia. Deafness calls for looking for mutations in Sox 10/CHD7/ILRD7 considering 38% association of former. Therapy should be individualized based on availability of pulsatile GnRH, cost factor and in recalcitrant cases kp therapy may be of use with kp mutations and NKB mutations.

References

[1]  Seminara, S.B., Hayes, F.J. and Crowley Jr., W.F. (1998) Gonadotropin-Releasing Hormone Deficienciesin the Human (Idiopathic Hypogonadotropin Hypogonadism and Kallman’s Syndrome) Pathophysiological and Genetic Considerations. Endocrine Reviews, 19, 521- 539.
[2]  Martin, K., Santoro, N., Hall, J., Filicori, M., Weirman, M. and Crowley Jr., W.F. (1990) Clinical Review 15: Management of Ovulatory Disorders with Pulsatile Gonadotropin Releasing Hormone. Journal of Clinical Endocrinology & Metabolism, 71, 1081A-1081G.
http://dx.doi.org/10.1210/jcem-71-5-1081
[3]  Bianco, S.D. and Kaiser, U.B. (2009) The Genetic and Molecular Basis of Idiopathic Hypogonadotropic Hypogonadism. Nature Reviews Endocrinology, 5, 569-576.
http://dx.doi.org/10.1038/nrendo.2009.177
[4]  Schwanzel-Fukuda, M. and Pfaff, D.W. (1989) Origin of Luteinizing Hormone Releasing Hormone Neurons. Nature, 338, 161-164.
http://dx.doi.org/10.1038/338161a0
[5]  Texeira, L., Guimior, F., Dode, C., Fallet-Bianco, C., Millar, R.P., Delezoide, A.L. and Hardelin, J.P. (2010) Defective Migration of Neuroendocrine GnRH Cells in Human Arrhinencephalic Conditions. Journal of Clinical Investigation, 120, 3668-3672.
http://dx.doi.org/10.1172/JCI43699
[6]  Franco, B., Guioli, S., Pragliola, A., Incern, B., Bardoni, B., Tonlorenzi, R., Carrozo, R., Mastrini, F., Pieretti, F., Taillon-Miller, P., Brown, C.J., Willard, H.F., Lawrence, C., Persico, M.G., Camerino, G. and Ballabio, A.A. (1991) Gene Deleted in Kallmann’s Syndrome Shares Homology with Neural Cell Adhesion and Axonal Path-Finding molecules. Nature, 353, 529-536.
http://dx.doi.org/10.1038/353529a0
[7]  Legouis, R., Hardelin, J.P., Levilliers, J., Claverie, J.M., Compain, S., Wunderle, V., Millaseau, P., LePaslier, D., Cohen, D., Caterina, D., Bougeleret, L., Delemarre-Van deWaal, H., Lutfalla, G., Weissenbach, J. and Petit, C. (1991) The Candidate Gene for the X Linked Kallmann Syndrome Encodes a Protein Related to Adhesion Molecules. Cell, 67, 423-435.
http://dx.doi.org/10.1016/0092-8674(91)90193-3
[8]  Dode, C., Levilliers, J., Dupont, J.M., De Paepe, A., Le Du, N., Soussi-Yanicostas, N., Coimbra, R.S., Delmaghani, S., Compain-Nouaille, S., Baverel, F., Pecheux, C., Le Tessier, D., Cruand, C., Delpech, M., Speleman, F., Vermuelen, S., Amalfitano, A., Bachelot, Y., Bouchard, P., Cabrol, S., Carel, J.C., Delemarre-vande Waal, H., Goulet-Salmon, B., Kottler, M.L., Richard, O., Sanchez-Franco, F., Saura, R., Young, J., Petit, C. and Hardelin, J.P. (2003) Loss of Function Mutations in FGFR1 Cause Autosomal Dominant Kallmanns Syndrome. Nature Genetics, 33, 463-465.
http://dx.doi.org/10.1038/ng1122
[9]  Falardeau, J., Chung, W.C., Beenken, A., Raivio, T., Plummer, E.F., Eliseenkova, A.V., Ma, J., Dwyer, A., Quinton, R., Na, S., Hall, J.E., Huot, C., Alois, N., Pearce, S.H., Cole, L.W., Hughes, V., Mohammadi, M., Tsai, P. and Pittelous, N. (2008) Dexreased FGF8 Signaling Causes Deficiency of Gonadotropin Releasing Hormone in Humans and Mice. Journal of Clinical Endocrinology & Metabolism, 118, 2822-2831.
[10]  Pitteloud, N., Acierno Jr, J.S., Meysing, A, Eliseenkova, A.V, Ma, J., Ibrahim, O.A., Metzger, D.L., Hayes, F.J., Dwyer, A.A., Hughes, V.A., Yialamas, M., Hall, J.E., Grant, E., Mohammadi, M. and Crowley Jr., W.F. (2006) Mutations in Fibroblast Growth Factor Receptor 1 Causes Both Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 103, 6281-6286.
http://dx.doi.org/10.1073/pnas.0600962103
[11]  Dode, C., Teixeira, L., Levvilliers, J., Fouveaut, C., Bouchard, P., Kottler, M.L., Lespinasse, J., Lienhart-Roussie, A., Mathew, M., Mierman, A., et al. (2006) Kalmann Syndrome: Mutations in the Genes Encoding Prokineticin 2 and Prokineticin Receptor 2. PLoS Gene, 2, e175.
http://dx.doi.org/10.1371/journal.pgen.0020175
[12]  Pitteloud, N., Zhang, C., Pognatelli, D., Li, J.D., Raivio, T., Cole, L.W., Plumer, L.W., Jacobson Dickman, E.E., Mellon, P.L., Zhou, Q.Y. and Crowley Jr., W.F. (2007) Loss of Function Mutation in the Prokineticin 2 Gene Causes Kallmann Syndromeand Normosmic Idiopathic Hypogonadotropic Hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 104, 17447-17452.
http://dx.doi.org/10.1073/pnas.0707173104
[13]  Cole, L.W., Sidis, Y., Zhang, C., Quinton, R., Plummer, L., Pignarelli, D., Hughes, V.A., Dwyer, A.A, Raivio, T., Hayes, F.J., Seminara, S.B., Huot, C., Alos, N., Speiser, P., Takeshita, A., et al. (2008) Mutations in Prokineticin 2 and Prokinrticin Receptor 2 Genes in Human Gonadotropin-Releasing Hormone Deficiency, Molecular Genetics and Clinical Spectrum. Journal of Clinical Endocrinology & Metabolism, 93, 3551-3559.
http://dx.doi.org/10.1210/jc.2007-2654
[14]  Leroy, C., Fouveaut, C., Leclercq, S., Jacquemont, S., Boullay, H.D., Lespinasse, J., Delpech, M., Dupont, J.M., Hardelin, J.P. and Dode, C. (2008) Biallelic Mutations in the Prokineticin Gene in Two Sporadic Case of of Kallmann Syndrome. European Journal of Human Genetics, 16, 865-868.
http://dx.doi.org/10.1038/ejhg.2008.15
[15]  Abreu, A.P., Trarbach, E.B., de Castro, M., Frade Costa, E.M., Versiani, B., Matias Baptista, M.T., Garmes, H.M., Mendonca, B.B. and Latronico, A.C. (2008) Loss of Function Mutations in the Genes Encoding Prokineticin 2 or Prokineticin Receptor 2 Cause Autosomal Recessive Kallmann Syndrome. Journal of Clinical Endocrinology & Metabolism, 93, 4113- 4118.
http://dx.doi.org/10.1210/jc.2008-0958
[16]  Sarfati, J., Guiochon-Mantel, A., Rondard, P., Arnulf, L., Garcio-Pinero, A., Wolczynski, S., Brailly-Tabard, S., Bidet, M., Ramos-Arroyo, M., Mathieu, M., Lienhardt-Roussie, A., Morgan, G., et al. (2010) Acomparative Phenotypic Study of Kallmann Syndrome Patients Carrying Monoallelic and Biallelic Mutations in the Prokineticin 2 or Prokineticin Receptor 2 Genes. Journal of Clinical Endocrinology & Metabolism, 85, 659-669.
http://dx.doi.org/10.1210/jc.2009-0843
[17]  Ogata, T., Fujiwara, I., Ogawa, F., Sato, N., Udaka, T. and Kosaki, S. (2006) Kallmann Syndrome Phenotype in a Female Patient with CHARGE Syndrome and CHD7 Mutation. Endocrine Journal, 53, 741-743.
http://dx.doi.org/10.1507/endocrj.K06-099
[18]  Jongmans, M.C., van Ravenswaaij-Arts, C.M., Pitteloud, N., Ogata, T., Sato, N., Claahsen-van der Grinden, H.I., van-den Donk, K., Seminara, S., Bergman, J.E.H., Brunner, H.G., Crowley Jr., W.F. and Hoefsloot, L.H. (2009) CHD7 Mutations in Patients Initially Diagnosed with Kallmann Syndrome—The Clinical Overlap with CHARGE Syndrome. Clinical Genetics, 75, 65-71.
http://dx.doi.org/10.1111/j.1399-0004.2008.01107.x
[19]  Kim, H.G., Kurth, I., Lan, F., Meliciani, I., Wenzel, W., Fom, S.H., Kang, G.B., Rosenberger, G., Tekin, M., Okata, M., Bick, D.P., Sherins, T.J., Walker, S.I., Shi, Y., Gusella, J.F. and Layman, L.C. (2008) Mutations in CHD7, Encoding a Chromatin Remodeling Protein, Causes Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome. American Journal of Human Genetics, 83, 511-519.
http://dx.doi.org/10.1016/j.ajhg.2008.09.005
[20]  Kim, H.G., Ahnm J.W., Kurth, I., Ullmann, R., Kim, H.T., et al. (2010) WDR11: A WD Protein That Interacts with Transcription Factor EMX1, Is Mutated in Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome. American Journal of Human Genetics, 87, 465-479.
http://dx.doi.org/10.1016/j.ajhg.2010.08.018
[21]  Hanchate, N.K., Giacobini, P., Lhullier, P., Prakash, J., Espy, C., Fouveaut, C., et al. (2012) SEMA3A: A Gene Involved in Axonal Pathfinding, Is Mutated in Some Patients with Kallmann Syndrome. PLoS Gene, 8, e1002896.
http://dx.doi.org/10.1371/journal.pgen.1002896
[22]  Young, J., Metay, C., Bouligand, J., Tou, B., Francou, B., Maione, L., et al. (2012) SEMA3A Seletion in a Family with Kallmann Syndrome Validates the Role of Semaphoring 3A in Human Puberty and Olfactory System. Human Reproduction, 27, 1460-1465.
http://dx.doi.org/10.1093/humrep/des022
[23]  Cariboni, A., Davidson, K., Rakic, S., Maggi, R., Parnavelas, J.G. and Ruhrberg, C. (2011) Defective Gonadotropin Releasing Hormone Neuron Migration in Mice Lacking SEMA3A Signaling through NRP1 and NRP2: Implications for the Aetiology of Hypogonadotropic Hypogonadism. Human Molecular Genetics, 20, 336-344.
http://dx.doi.org/10.1093/hmg/ddq468
[24]  Kansakoski, J., Fagerholm, R., Laitinen, E.M., Vaaralahti, K., Hackman, P., Pitteloud, N., Raivio, T. and Tommisia, J. (2014) Mutation Screening of SEMA3A and SEMA7A in Patients with Congenital Hypogonadotropic Hypogonadism. Pediatric Research, 75, 641-644.
http://dx.doi.org/10.1038/pr.2014.23
[25]  Balasubramaniam, R., Plummer, L., Sidis, Y., Pitteloud, N., Cecila, N., Zhou, Q.Y. and Crowley, Jr W.F. (2011) The Puzzles of the Pronineticin 2 Pathway in Human Reproduction. Molecular and Cellular Endocrinology, 346, 44-50.
http://dx.doi.org/10.1016/j.mce.2011.05.040
[26]  Martin, C., Balasubramanium, R., Dwyer, A.A., Au, M.G., Sidis, Y., Kaiser, U.B., Seminara, S.B., Pitteloud, N., Zhou, Q.Y. and Crowley Jr W.F. (2011) The Role of the Prokineticin 2 Pathway in Human Teproduction: Evidence from the Study of Human and Murine Mutations. Endocrine Reviews, 32, 225-246.
http://dx.doi.org/10.1210/er.2010-0007
[27]  Kochar, Kaur, K., Allahbadia, G.N. and Singh, M. (2013) An Update on the Role of Prokineticins in Human Reproduction-Potential Therapeutic Applications. Open Journal of Genetics, 3, 201-215.
http://dx.doi.org/10.4236/ojgen.2013.33023
[28]  Dode, C. and Rondard, P. (2013) PROK2/PROKR2 Signaling and Kallmann Syndrome. Frontiers in Endocrinology (Lausanne), 4, 19.
http://dx.doi.org/10.3389/fendo.2013.00019
[29]  Ragancokoya, D., Rocca, E., Oonk, A.M.M., Schultz, H., Rohde, E., Bednarsch, J., Feenstra, I., Pennings, R.J., Wende, H. and Garratt, A.N. (2014) TSHZ1-Dependent Gene Regulation Is Essential for Olfactory Bulb Development and Olfaction. Journal of Clinical Investigation, 124, 1224-1227.
http://dx.doi.org/10.1530/EJE-13-0419
[30]  Sarfati, J., Fouveat, C., Leroy, C., Jeanpierre, M., Hardelin, J.P. and Dode, C. (2013) Greater Prevalence of PROKR2 Mutations in Kallmann Syndrome Patients from Maghreb than in European Patients. European Journal of Endocrinology, 169, 805-809.
http://dx.doi.org/10.1530/EJE-13-0419
[31]  Chen, D.N., Ma, Y.T., Liu, H., Ziou, Q.Y. and Li, J.D. (2014) Functional Rescue of Kallmann Syndrome-Associated PKR2 Receptor Mutants Deficient in Trafficking. Journal of Biological Chemistry, 289, 15518-15526.
http://dx.doi.org/10.1074/jbc.M114.556381
[32]  Salian-Mehta, S., Xu, M., Knox, A.J., Plummer, A.L., Slavov, D., Taylor, M., Bevers, S., Hodgers. R.S., Crowley Jr., W.F. and Wierman, M.E. (2014) Functional Consequences of AXL Sequence Variants in Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism, 99, 1452-1460.
http://dx.doi.org/10.1210/jc.2013-3426
[33]  Newbern, K., Natrajan, N., Goo-Kim, H., Chorich, L.P., Halvorson, L.M., Cameron, R.S. and Layman, L.C. (2013) Identification of HESX1 Mutations in Kallmann Syndrome. Fertility and Sterility, 99, 1831-1837.
http://dx.doi.org/10.1016/j.fertnstert.2013.01.149
[34]  Niederberger, C. (2014) RE, Identification of HESX1 Mutations in Kallmanns Syndrome. Journal of Urology, 191, 1081.
http://dx.doi.org/10.1016/j.juro.2014.01.067
[35]  Hardelin, J.P. and Dode, C. (2008) The Complex Genetics of Kallmann Syndrome, KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sexual Development, 2, 181-193.
http://dx.doi.org/10.1159/000152034
[36]  de Roux, N., Genin, E., Carel, J.C., Matsuda, F., CusSain, J.L. and Milgrom, E. (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
http://dx.doi.org/10.1073/pnas.1834399100
[37]  Pallais, J.C., Bo-Abbas, Y., Pitteloud, N., Crowley Jr., W. and FandSeminara, B. (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.
http://dx.doi.org/10.1016/j.mce.2006.04.019
[38]  Topaloglu, A.K., Tello, J.A., Kotan, L.D., Ozbek, M.N., Yilmaz, M.B., Erdogan, S., Gurbuz, F., Terniz, F., Millar, R.P. and Yuksel, B. (2012) Inactivating KISS1 Mutationsand Hypogonadotropic Hypogonadism. The New England Journal of Medicine, 366, 629-635.
http://dx.doi.org/10.1056/NEJMoa1111184
[39]  Topaloglu, A.K., Reimann, F., Guclu, M., Yalin, A.S., Kotani, L.D., Porter, K.M.Serin, A,Mungan, N.O,Cook, J.R,Ozbek, M.N,Imamoglu, S, Akalin, N.S., et al. (2009) TAC3 andTACR3 Mutations in Familial Hypogonadotropic Hypogonadism Reveal a Key Role for Neurokinin B in the Central Control of Reproduction. Nature Genetics, 41, 354-358.
http://dx.doi.org/10.1038/ng.306
[40]  Bouligard, J., Ghervan, C., Tello, J.A., Brailly-Tabard, S., Salenave, S., Chanson, P., Lombes, P., Millar, R.P., Guiochon-Mantel, A. and Young, J. (2009) Isolated Familial Hypogonadotropic Hypogonadism ana a GnRH 1 Mutation. The New England Journal of Medicine, 360, 2742-2748.
http://dx.doi.org/10.1056/NEJMoa0900136
[41]  Chan, Y.M., de Guillebon, A., Lang-Muritano, M., Plummer, L., Cerrato, F., Tsiaras, F., Gaspert, A., Lavoie, H.B., Wu, C.H., Ceowley Jr., W.F., Amory, J.K., Pitteloud, N., Seminara, S.B. and Gn, R.H. (2009) 1 Mutations in Patients with Idiopathic Hypogonaditropic Hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 106, 11703-11708.
http://dx.doi.org/10.1073/pnas.0903449106
[42]  Tello, J.A., Newton, C.L., Bouligard, J., Guiochon-Mantel, A., Millar, R.P. and Young, J. (2012) Congenital Hypogonadotropic Hypogonadism Due to GnRH Receptor Mutations in Three Brothers Reveal Sires Affecting Conformation and Coupling. PLoS ONE, 7, e38456.
http://dx.doi.org/10.1371/journal.pone.0038456
[43]  Sykiotis, G.P., Plummer, L., Hughes, V.A., Au, M., Durrani, S., Young, S.N., Dwyer, A.A., Quinton, R., Hall, J.E., Gusella, J.F., Seminara, S.B., Crowley Jr., W.F. and Pitteloud, N. (2010) Oligogenic Basis of Isolated Gonadotropin-Releasing Hormone Deficiency. Proceedings of the National Academy of Sciences of the United States of America, 107, 15140- 15144.
http://dx.doi.org/10.1073/pnas.1009622107
[44]  Lewkowitz-Shupntoff, H.M., Hughes, V.A., Plummer, L., Au, M.G., Doty, R.L., Seminara, S.B., Chan, Y.M., Potteloud, N., Crowley Jr., W.F. and Balasubramaniam, R. (2012) Olfactory, Phenotypic Spectrums in Idiopathic Hypogonadotropic Hypogonadism, Pathophysiological and Genetic Implications. Journal of Clinical Endocrinology & Metabolism, 97, E136-E144.
http://dx.doi.org/10.1210/jc.2011-2041
[45]  Valetti, E.D., Vazzat, S., Rochira, V., Granata, A., Madeo Genovesic, M., Pignatti, E., Marino, M., Carani, C. and Simon, M. (2013) Prevalence of Olfactory and Other Developmental Anomalies in Patients with Central Hypogonadotropic Hupogonadism. Frontiers in Endocrinology (Laussanne), 4, 70.
[46]  Plana, A.M., Villanueva, C., Laccourreye, O., Bonfils, P. and de Roux, N. (2013) PROKR2 and PROK2 Mutations Cause Isolated Congenital Anosmia without Gonadotropin Deficiency. European Journal of Endocrinology, 168, 31-37.
http://dx.doi.org/10.1530/EJE-12-0578
[47]  Qyanor, S.D., Kim, G.H., Cappello, E.H., Williams, T., Chorich, L.P., Bick, D.P., Sherins, R.J. and Laymans, L.C. (2011) The Prevalence of Digenic Mutations in Patients with Normosmic Hypogonadotropic Hypogonadism and Kalmmann Syndrome. Fertility and Sterility, 96, 1424-30e6
[48]  Chung, W.C., Moyle, S.S. and Tsai, P.S. (2008) Fibroblast Growth Factor 8 Signaling through Fibroblast Growth Factor Receptor 1 Is Required for the Emergence of Gonadotropin Releasing Hormone Neurons. Endocrinology, 149, 4997-5003.
http://dx.doi.org/10.1210/en.2007-1634
[49]  Ladher, R.K., Weight, T.J., Moon, A.M., Mansour, S.A. and Schoenwolf, G.C. (2005) FGF8 Initiares Inner Ear Induction in Chick and Mouse. Genes & Development, 19, 603-615.
http://dx.doi.org/10.1101/gad.1273605
[50]  Martinez-Morales, J.R., Del Bene, F., Nica, G., Hammerschmidt, M., Bovolenta, P. and Willbrodt, J. (2005) Differentiation of the Vertebrate Retina Is Coordinated by an FGF Signaling Center. Developmental Cell, 8, 565-574.
http://dx.doi.org/10.1016/j.devcel.2005.01.022
[51]  Perantoni, A.O., Timofeeva, O., Naillat, F., Richman, C., Pajni-Underwood, S., Wilson, C., Vainio, S., Dove, L.F. and Lewandoski, M. (2005) Inactivation of FGF8 in Early Mesoderm Reveals an Essential Role in Kidney Development. Development, 132, 3859-3871.
http://dx.doi.org/10.1242/dev.01945
[52]  Lewandoski, M., Sun, X. and Martin, G.R. (2000) FGF8 Signaling from the AER Is Essential for Normal Limb Development. Nature Genetics, 26, 460-463.
http://dx.doi.org/10.1038/82609
[53]  Miraoui, H., Dwyer, A. and Pitteloud, N. (2011) Role of Fibroblast Growth Factor (FGF) Signaling in the Neuroendocrine Control of Human Reptoduction. Molecular and Cellular Endocrinology, 346, 37-43.
http://dx.doi.org/10.1016/j.mce.2011.05.042
[54]  Tornberg, J., Sykiotis, G.P., Keefe, K., Plummer, L., Hoang, X., Hall, J.E., Quinton, R., etal. (2011) Heparan sulfate 6-O-Transferase 1: A Gene Involved in Extracellular Sugar Modifications Is Mutated in Patients with Idiopathic Hypogonadsotropic Hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 108, 11524-11529.
http://dx.doi.org/10.1073/pnas.1102284108
[55]  Miraoui, H., Dwyer, A.A., Sykiotis, G.P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T.H., Dworzynski, P., Keefe, K., Niedziela, M., Raivio, T., Crowlry, W.T., Seminara, S.B., Quinton, R., Hughes, V.A., Kumanov, P., Young, J., Yialamas, M.A., Hall, J.E., van-Vliet, G., Chanoine, J.P., Rubenstein, J., Mohammadi, M., Tsai, P.S., Sidis, Y., Lage, K. and Pitteloud, N. (2013) Mutations in FGF17, IL17RD, DUSP6, SPRY4 and FLRT3 Are Iudentifird in Indiciduals wirh Congenital Hypogonadotropic Hypogonadism. American Journal of Human Genetics, 92, 725-743.
http://dx.doi.org/10.1016/j.ajhg.2013.04.008
[56]  Abhazonov, A., Tabin, C.J. (2004) Shh and FGF8 Act Synergistically to Drive Cartlage Outgrowth during Cranial Development. Developmental Biology, 273, 134-148.
http://dx.doi.org/10.1016/j.ydbio.2004.05.028
[57]  Bajpai, R., Chen, D.A., Rada-Iglesia, A., Zhang, J., Xiong, Y., Helins, J., Chang, C.P., Zhao, Y. and Swigut, T. and Wysocka, J. (2010) CHD7 Cooperates with PBAF to Control Multipotent Neural Crest Formation. Nature, 463, 958-962.
http://dx.doi.org/10.1038/nature08733
[58]  Creuzet, S., Schuler, B., Couly, G. and LeDouarin, N.M. (2004) Reciprocal Relationship between FGF8 and Neural Crest Cells in Fascial and Forebrain Development. Proceedings of the National Academy of Sciences of the United States of America, 101, 1843-1847.
http://dx.doi.org/10.1073/pnas.0400869101
[59]  Kawauchi, S., Shou, J., Santos Hebert, J.M., McConell, S.K., Mason, I. and Calof, A.L. (2005) FGF8 Expression Defines Amorphogenetic Center Required for Olfactory Neurogenesis Ans Nasal Cavity Development in the Mouse. Development, 132, 5211-5223.
http://dx.doi.org/10.1242/dev.02143
[60]  Trarbach, E.B., Abreu, A.P., Silveira, L.F., Garmes, H.M., Baptista, M.T., Teles, M.G., Costa, E.M., Mohammadi, M., Pitelloud, N., Mendonca, B.B. and Letronico, A.C. (2010) Nonsense Mutations in FGF8 Gene Causing Different Degrees of Human Gonadotropin-Releasing Deficiency. Journal of Clinical Endocrinology & Metabolism, 95, 3491-3496.
http://dx.doi.org/10.1210/jc.2010-0176
[61]  Forni, P.E., Burds, C.T., Melvin, V.S., Williams, T. and Wray, S. (2011) Neural Crest and Ectodermal Cells Intermix in the Nasal Placode to Give Rise to GnRH-1 Neurons, Sensory Neurons and Olfactory Ensheathing Cells. The Journal of Neuroscience, 31, 6915-6927.
http://dx.doi.org/10.1523/JNEUROSCI.6087-10.2011
[62]  Carter, L.A., Macdonald, J.L. and Roskams, A.J. (2004) Olfactory Horizontal Basal Cells Demonstrate a Conserved Multipotent Progenitor Phenotype. The Journal of Neuroscience, 24, 5670-5683.
http://dx.doi.org/10.1523/JNEUROSCI.0330-04.2004
[63]  Williams, M.S. (2005) Speculations on the Pathogenesis of CHARGE Syndrome. American Journal of Medical Genetics Part A, 133A, 318-325.
http://dx.doi.org/10.1002/ajmg.a.30561
[64]  Forni, P.E., Bharti, K., Flannery, E.M., Shimogori, T. and Wray, S. (2013) The Indirect Role of Fibroblast Growth Factor-8 in Defining Neurogenic Niches of the Olfactory/GnRH Systems. The Journal of Neuroscience, 33, 19620-19634.
http://dx.doi.org/10.1523/JNEUROSCI.3238-13.2013
[65]  Schultz, Y., Wehner, P., Opitz, L., Salinas-Riester, G., Bongers, E.M., van Ravenswaaij-Arts, C.M., Wincent, J., Schoumans, J., Kohlhase, J., Borchers, A. and Pauli, S. (2014) CHD7, the Gene Mutated in CHARGE Syndrome: Regulates Genes Involved in Neural Crest Cell Guidance. Human Genetics, 133, 997-1009.
http://dx.doi.org/10.1007/s00439-014-1444-2
[66]  Costa-Barbosa, F.A., Balasubramaniam, R., Keefe, K.W., Shaw, N.D., Al-Tassan, N., Plummer, L., Dwyer, A.A., Buck, C.L., Choi, C.H., Seminara, D.B., Quinton, R., Monies, D., Meyer, D., Hall, J.E., Pitteloud, N. and Crowley Jr., W.F. (2013) Prioritizing Geneting Testing in Patients with Kallmann Syndrome Using Clinical Phenotypes. Journal of Clinical Endocrinology & Metabolism, 98, E943-E953.
http://dx.doi.org/10.1210/jc.2012-4116
[67]  Dode, C. and Hardelin, P. (2010) Clinical Genetics of Kallmanns Syndrome. Annales d Endocrinologie (Paris), 71, 149-157.
http://dx.doi.org/10.1016/j.ando.2010.02.005
[68]  Fideleff, H.L., Bouquete, H.R., Suarez, M.G. and Azaretzky, M. (2009) Prolactinomas in Children and Adolescents. Hormone Research, 72, 197-205.
http://dx.doi.org/10.1159/000236081
[69]  Jagabbathan, J., Dumont, A.S. and Jane Jr., J.A. (2006) Diagnosis and Management of Pediatric Sellar Lrsions. Frontiers of Hormone Research, 34, 83-104.
http://dx.doi.org/10.1159/000091574
[70]  Young, J. (2007) Endocrine Consequences of Haemochromatosis. Presse Médicale, 36, 1319-1325.
http://dx.doi.org/10.1016/j.lpm.2007.01.041
[71]  Ozgor, B. andSelimodiu, M.A. (2010) Coeliac Disease and Reproductive Disorders. Scandinavian Journal of Gastroenterology, 45, 395-402.
http://dx.doi.org/10.3109/00365520903508902
[72]  Farooqo, J.S., Wangensteen, T., Collins, S., Kimber, W., Matarese, G., Keoh, G.M., Lank, E., Moottommlev, B., Lopez-Fernandez, J., Ferraz-Amaro, I., Dattani, M.T., Ercan, O., Mvhre, A.G., Retterstol, L., Stanhoe, R., Edoe, J.A., McKenzie Undlien, D.E. and O’Rahilly, S. (2007) Clinical and Molecular Genetic Spectrum of Genetic Spectrum of Congenital Deficiency of the Leptin Receptor. The New England Journal of Medicine, 356, 237-247.
http://dx.doi.org/10.1056/NEJMoa063988
[73]  Lin, L., Gu, W.X., Ozisik, G., To, W.S., Owen, C.J., Jameson, J.L. and Achermann, J.C. (2006) Analysis of DAX 1 (NROB1) and steroidogenic Factor 1 (SF1/Ad4BP, NR5A1) in Children and Adults with Primary Adrenal Failure: Ten Years of Experience. Journal of Clinical Endocrinology & Metabolism, 91, 3048-3054.
http://dx.doi.org/10.1210/jc.2006-0603
[74]  Netchine, I., Sobrier, M.L., Krude, H., Schnabel, D., Maohne, M., Marcos, E., Duriez, B., Cacheux, V., Moers, A., Grossns, M., Gruters, A. and Amselem, S. (2000) Mutations in LHX3 Result in a New Syndrome Revealed by Combined Pituitary Hormone Deficiency. Nature Genetics, 25, 182-186.
http://dx.doi.org/10.1038/76041
[75]  Pinto, G., Abadie, V., Mesnade, R., Blustain, J., Cabrol, S., Amiel, J., Hertz-Pennier, L., Bertrand, A.M., Lyonnet, S., Rappaport, E. and Netchine, I. (2005) CHARGE Syndrome Includes Hypogonadotropic Hypogonadism and Abnormal Olfactory Bulb Development. Journal of Clinical Endocrinology & Metabolism, 90, 5621-5626.
http://dx.doi.org/10.1210/jc.2004-2474
[76]  Rottembouro, D., Linglart, A., Adamsbaum, C., Lahlou, N., Teinturier, C., Bougneres, P. and Carel, J.C. (2008) Gonadotrophic Status in Adolescent s with Pituitary Stalk Interruption Syndrome. Clinical Endocrinology, 69, 105-111.
http://dx.doi.org/10.1111/j.1365-2265.2007.03155.x
[77]  Revnaud, R., Gueydan, M., Saveanu, A., Vallette-Ksic, S., Enjalbert, A., Beue, T. and Barlier, A. (2006) Genetic Screening of Combined Pituitary Hormone Deficiency Experience in 195 Patients. Journal of Clinical Endocrinology & Metabolism, 91, 3329-3336.
http://dx.doi.org/10.1210/jc.2005-2173
[78]  Harrington, J. and Palmert, M.R. (2012) Clinical Review, Distinguishing Constitutional Delay of Growrh and Puberty from Isolated Hypogonadotropic Hypogonadism, Crotical Appraisal of Available Diagnostic Tests. Journal of Clinical Endocrinology & Metabolism, 97, 3056-3067.
http://dx.doi.org/10.1210/jc.2012-1598
[79]  Sedimeyer, I.L. and Palmert, M.R. (2002) Delayed Puberty: Analysis of a Large Case Series from an Academic Center. Journal of Clinical Endocrinology & Metabolism, 87, 1613-1620.
http://dx.doi.org/10.1210/jcem.87.4.8395
[80]  Pitteloud, N., Hayes, F.J., Boeoole, P.A., DeCruz, S., Seminara, S.B., McLaughlin, D.T. and Crowley Jr., W.F. (2002) The Role of Prior Pubertal Development, Biochemical Markers of Testicular Maturation and Genetics in Elucidating the Phenotypic Herterogeneity of Idiopathic hypogonadotrophic hypogonadism. Journal of Clinical Endocrinology & Metabolism, 87, 152-160.
http://dx.doi.org/10.1210/jcem.87.1.8131
[81]  Salenave, S., Chandon, P., Bry, H., Pugeat, M., Cabrol, S., Murat, A., Lecomte, P., Braiily, S., Hardelin, J.P., Dode, C. and Young, J. (2008) Kallmann’s Syndrome: A Comparison of the Reproductive Phenotypes in Men Carrying KAL1 and FGR1/KAL2 Mutations. Journal of Clinical Endocrinology & Metabolism, 93, 758-763.
http://dx.doi.org/10.1210/jc.2007-1168
[82]  Coutant, R., Biette-Demrneix, E., Bouvattier, C., Bouhours-Nouet, N., Gatelais, F., Dufresne, S., Rouleau, S. and Lahlou, N. (2010) Baseline Inhibin B and Anti Mullerian Hormone Measurements for Diagnosis of Hypogonadotropic Hypogonadism in Boyswith Delayed Puberty. Journal of Clinical Endocrinology & Metaboism, 95, 5225-5232.
http://dx.doi.org/10.1210/jc.2010-1535
[83]  De Luca, F., Argente, J., Cavallo, L., Ceowne, E., Delemarre-Vande Waal, HA., De Sanctis, C., Di Maio, S., Noriavaara, E., Oostdjik, W., Severi, F., ToninI, G., Trifiro, G., Voorhoeve, P.G. and Wu, F. (2001) Management of Puberty in Constitutional Dalay of Growth and Puberty. International workshop on Management of Puberty for Optimum Auxological Results, Journal of Pediatrics, 14, 953-957.
[84]  Young, J. (2012) Approach to the Male Patient with Congenital Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism, 97, 707-718.
http://dx.doi.org/10.1210/jc.2011-1664
[85]  Manara, R., Salvalaggio, A., Favaro, A., Palumbo, V., Citton, V., Elefante, A., Brunetti, A., Di Salle, F., Bonarini, G. and Sinisi, A.A. and Kallmann Syndrome Neuroradiological Study Group (2014) Brain Changes in Kallmann Syndrome. American Journal of Neuroradiology, 35, 1700-1706.
http://dx.doi.org/10.3174/ajnr.A3946
[86]  Chew, S., Balasubramaniam, R., Chan, W.M., Kang, P.B., Andrews, C., Webb, B.D., Mackinson, S.E., Oystrreck, D.T., Rankin, J., Crawford, T.O., Geraghty, M., Pomeroy, S.L., Crowlryt Jr., W.F., Jabs, E.W., Hunter, D.G., Grant, P.E. and Engle, E.C. (2013) A Novel Syndrome Caused by the E410K Amino acid Substitution in the Neuronal β-Tubulin Isotype 3. Brain, 136, 522-535.
http://dx.doi.org/10.1093/brain/aws345
[87]  Raivio, T., Avbeli, M., McCabe, M.J., Romero, D.J., Swyer, A.A., Tommiska, J., Sykiotis, G.P., Gregory, I.C., Diaczok, D., Tziaferi, V., Elting, M.W., Padidela, M.W., Plummer, L., Martin, C., Feng, B., Zhang, C., Zhou, Q.Y., Chen, H., Mohammedi, M., Quinton, R., Sidis, Y., Radovick, S., Dattani, M.T. and Pitelloud, N. (2012) Genetic Overlap in Kallmann Syndrome, Combined Pituitary Hormone Deficiency, and Septo Optic Dysplasia. Journal of Clinical Endocrinology & Metabolism, 97, E694-E699.
http://dx.doi.org/10.1210/jc.2011-2938
[88]  McCabe, M.J., Gaston-Massuet, C., Gregory, L.C., Alatzoglu, K.S., Tziaferi, V., Sbai, O., Rondard, P., Masumoto, K.H., Nagano, M., Shigeyoshi, Y., Pfiefer, M., Hulse, T., Buchanan, C.R., Potteloud, N., Martinez-Barbera, J.P. and Dattani, M.T. (2013) Variations in PROKR2 but Not PROK2, Are Associated with Hypopituitarism and Septo-Optic Dysplasia. Journal of Clinical Endocrinology & Metabolism, 98, E547-E557.
http://dx.doi.org/10.1210/jc.2012-3067
[89]  McCabe, M.J., Alatzoglu, K.S. and Dattani, M.T. (2011) Septo-Optic Dysplasia and Other Midline Defects: The Role of Transcription Factors, HESX1 and beyond. Best Practice & Research Clinical Endocrinology & Metabolism, 25, 115-124.
http://dx.doi.org/10.1016/j.beem.2010.06.008
[90]  Cohen Jr., M.M. (2006) Holoprosencephaly, Clinical, Anatomic, and Molecular Dimensions. Birth Defects Research Part A: Clinical and Molecular Teratology, 76, 658-673.
http://dx.doi.org/10.1002/bdra.20295
[91]  Dubourg, C., Teixeira, L., Levilliers, J., Fouveaut, C., Bouchard, P., et al. (2007) Holoprosencephaly. Orphanet Journal of Rare Diseases, 2, 8.
http://dx.doi.org/10.1186/1750-1172-2-8
[92]  Vaaralahti, K., Raivio, T., Koivu, R., Valanne, L., Laitinen, M. and Tommiska, J. (2012) Genetic Overlap between holoprosencephaly and Kallmann Syndrome. Molecular Syndromology, 3, 1-5.
http://dx.doi.org/10.1159/000338706
[93]  Castaneyra-Perdono, A., Casraneyra-Ruiz, L., Gonzalez-Marrero, I., Castaneyra-Ruiz, A., GonzalezoToledo, J.M., Castaneyra-Ruiz, M. and Carmona-Calero, E.M. (2014) Early Treatment of Kallmann Syndrome Mayorevent Eunuchoid Appearance and Behavior. Medical Hypotheses, 82, 74-76.
http://dx.doi.org/10.1016/j.mehy.2013.11.011
[94]  Hoffman, A.R. and Crowley Jr., W.F. (1982) Induction of Puberty in Men by Long-Term Pulsatlle Administration of Low Dose Gonadotropin Releasing Hormone. The New England Journal of Medicine, 307, 1237-1241.
http://dx.doi.org/10.1056/NEJM198211113072003
[95]  Raivio, T., Wikstrom, M. and Dunkel, L. (2007) Treatment of Gonadotropin Deficient Boys with Recombinant Human FSH, Long Term Observation and Outcome. European Journal of Endocrinology, 156, 105-111.
http://dx.doi.org/10.1530/eje.1.02315
[96]  Quinton, R., Cheow, H.K., Tymms, D.J., Bouloux, P.M., Wu, F.C. and Jacobs, H.C. (1999) Kallmann’s Syndrome: Is It Always for life? Clinical Endocrinology, 50, 481-485.
http://dx.doi.org/10.1046/j.1365-2265.1999.00708.x
[97]  Raivio, T., Falardeau, J., Dwyer, A., Quinton, R., Hayes, F.J., Hughes, V.A., Cole, L.W., Pearce, S.H., Lee, H., Boepple, P., Crowley Jr., W.F. and Pitteliud, N. (2007) Reversal of Idiopathic Hypogonadotropic Hypogonadism. The New England Journal of Medicine, 357, 863-873.
http://dx.doi.org/10.1056/NEJMoa066494
[98]  Sidhoum, V.F., Chan, Y.M., Lipincott, M.F., Balasubramaniam, R., Quinton R., Plummel, L., Dwyer, A., Pitelloud, N., Hayes, F.J., Martin, K.A., Boepple, P.A. and Seminara, S.B. (2013) Reversal and Relapse of Hypogonadotropic Hypogonadism, Resilience and Fragility of the Reproductive Neuroendocrine System. Journal of Clinical Endocrinology & Metabolism, 99, 861-870.
http://dx.doi.org/10.1210/jc.2013-2809
[99]  Bouvattier, C., Tauber, M., Jouret, B., Chaussan, J.L. and Rochiccioli, P. (1999) Gonadotropic Treatment of Hypogonadotropic Hypogonadal Adolescents. Journal of Pediatric Endocrinology and Metabolism, 12, 339-344.
[100]  Gong, W. and Gao, X.C. (2013) Clinical Diagnosis and Treatment of Male Kallmann Syndrome. National Journal of Andrology, 19, 1111-1114.
[101]  Pitelloud, N., Hayes, F.J., Boepple, P.A., Lee, H. and Crowley Jr., W.F. (2002) Predictors of Outcome of Longterm GnRH Therapy in men with Idiopathic Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabo-ism, 87, 4128-4141.
http://dx.doi.org/10.1210/jc.2002-020518
[102]  Sykiotis, G.P., Hoang, X.H., Avberg, M., Hayes, F.J., Thambundit, A., Dwyer, A., Au, M., Plummer, L., Crowley Jr., W.F. and Pitelloud, N. (2010) Congenital Idiopathic Hypogonadotropic Hypogonadism: Evidence and Defects of the Hypothalamus, Pituitary, and Testis. Journal of Clinical Endocrinology & Metabolism, 95, 3019-3027.
http://dx.doi.org/10.1210/jc.2009-2582
[103]  Sinisi, A.A., Asci, R., Bellastella, G., Maione, L., Esposito, D., Elefante, A., DeBellis, A., Bellastella, A. and Iolascon, A. (2008) Homozygous Miutation in the Prokineticin Receptor 2 Gene (Val 274Asp) presenting as Reversible Kallmann Syndrome and Persistent Oligozoospermia: Case Report. Human Reproduction, 23, 2380-2384.
http://dx.doi.org/10.1093/humrep/den247
[104]  Dwyer, A.A., Sykiotis, G.P., Hayes, F.J., Boepple, P.A., Lee, H., Loughlin, K.R., Dym, M., Sluss, P.M., Crowley Jr., W.F. and Pitelloud, N. (2013) Trial of Recombinant Follicle-Stimulating Hormone Pretreatment in Patients with Congenital Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism, 98, E1790-E1795.
http://dx.doi.org/10.1210/jc.2013-2518
[105]  Pitelloud, N., Thambundit, A., Dwyer, A.A., Falardeau, J.L., Plummer, L., Caronia, L.M., Hayes, F.J., Lee, H., Boepple, P.A. and Crowley Jr., W.F. (2009) Role of Seminiferous Tubular Development in Determining the FSH vs LH Responsiveness to GnRH in Early Sexual Maturation. Neuroendocrinology, 90, 260-268.
http://dx.doi.org/10.1159/000245383
[106]  Trabados, S., Maione, L., Bry-Gauillard, H., Affres, H., Salenave, S., Sarfati, J., Bouvattier, C., Delemer, B., Chapson, P., Le Bouc, Y., Brailly-Tabard, S. and Young, J. (2014) Insulin-Like Peptide-3 (INSL-3) in Men with Congenital Hypogonadotropic Hypogonadism/Kallmann Syndrome and Effects of Different Modalities of Hormonal Treatment, Asingle—Center Study of 281 Patients. Journal of Clinical Endocrinology & Metabolism, 99, E266-E275.
[107]  Trabados, S., Lamothe, S., Maione, L., BouvaTtier, C., Sarfati, J., Brailly-Tabard, S. and Young, J. (2014) Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome as Models for Studying Hormonal Regulation of Human Testicular Endocrine Functions. Annales d Endocrinologie, 75, 79-87.
http://dx.doi.org/10.1016/j.ando.2014.04.011
[108]  Shaw, N.D., Seminara, S.B., Welt, C.K., Au, M.G., Plummer, L., Hughes, V.A., Dwyer, A.A., Martin, K.A., Quinton, R., Mericq, V., Merino, P.M., Gusella, J.F., Crowley Jr., W.F., Pitelloud, N. and Hall, J.E. (2011) Expanding the Phenotype and Genotype of Female GnRH Deficiency. Journal of Clinical Endocrinology & Metabolism, 96, E566-E576.
http://dx.doi.org/10.1210/jc.2010-2292
[109]  Pallais, J.C., Au, M., Pitelloud, N., et al. (2011) Kallmann Syndrome. GeneReviews, Online.
http://wwwnchnih
[110]  Bramswig, J., Fabregues, F., Carmona, F., et al. (2009) Disorders of Pubertal Development. Deutsches ?rzteblatt International, 106, 295-303.
[111]  Tsimaris, T., Vrachnis, N., Hiodromaiti, Z., et al. (2012) Long Term Follow up of Adolescent and Young Females with Hypetgonadotropic Hypogonadotropism. International Journal of Endocrinology, 73, 2367-2373.
[112]  Hoffman, J., Watzlawik, M. and Richter-Appelt, H. (2013) Living with Kallmann Syndrome—Analysis of Subjective Expeerience Reports from Women. Geburtshilfe Frauenheilkd, 73, 111-120.
[113]  Messinis, I.E. (2005) Ovulation Induction: A Mini Review. Human Reproduction, 20, 2688-2697.
http://dx.doi.org/10.1093/humrep/dei128
[114]  Knobil, E., Plant, T.M, Wildt, L., Belchetz, P.E. and Marshall, G. (1980) Controlof the Rhesus Monkey Menstrual Cycle, Permissive Role of Hypothalamic Gonadotrophic Gonsdotropin Releasing Hormone. Science, 207, 1371-1373.
http://dx.doi.org/10.1126/science.6766566
[115]  Belchetz, E., Plant, T.M., Nakai, Y., Keogh, E.J. and Knobil, E. (1978) Hypophyseal Responses to Continuous and Intermittent Delivery of Hypothalamic Gondotropin Releasing Hormone. Science, 212, 631-633.
http://dx.doi.org/10.1126/science.100883
[116]  Balasch, C., Salvatori, M., Regnani, G., et al. (2009) Ovarian Luteinizing Hormone Priming Preceding Follicle Stimulating Hormone Stimulation, Clinical and Endocrine Effects in Women with Long Term Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism, 73, 2367-2373.
http://dx.doi.org/10.1210/jc.2009-0262
[117]  Abel, B.S., Shaw, N.D., Brown, J.M., Adams, J.M., Alati, T., Martin, K.A., Pitelloud, N., Seminara, S.B., Plummer, L., Pignatelli, D., Crowley Jr., W.F., Welt, C.K. and Hall, J.E. (2013) Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Gentype in Women with Isolated Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism, 98, E206-E216.
http://dx.doi.org/10.1210/jc.2012-3294
[118]  Bouvattier, C., Maione, L., Bouligard, J., Dode, C., Guiochon-Mantel, A. and Young, J. (2011) Neonatal Gonadotropin Therapy in Male Congenital Hypogonadotropic Hypogonadism. Nature Reviews Endocrinology, 8, 172-182.
http://dx.doi.org/10.1038/nrendo.2011.164
[119]  Main, K.M., Schmidt, I.M. and Skakkeberk, N.E. (2002) Early Postnatal Treatment of Hypogonaditropic Hypogonadism with Recombinant Human FSH and LH. European Journal of Endocrinology, 146, 75-79.
http://dx.doi.org/10.1530/eje.0.1460075
[120]  Main, K.M., Schmidt, I.M. and Skakkeberk, N.E. (2000) Apossible Role for Reproductive Hormones in Newborn Boys, Progressive Hypogonadism without the Postnatal Testosterone Peak. Journal of Clinical Endocrinology & Metabolism, 85, 4905-4907.
http://dx.doi.org/10.1210/jcem.85.12.7058
[121]  Bouoneres, P., Francois, M., Pantalone, L., Rodrique, D., Bouvattier, C., Demesteere, E., Roger, D. and Lahlou, N. (2008) Effects of an Early Postnatal Treatment of Hypogonaditropic Hypogonadism with a Continuous Subcutaneous Infusion of Recombinant Follicle Stimulating Hormone and Luteinizing Hormone. Journal of Clinical Endocrinology & Metabolism, 93, 2202-2205.
http://dx.doi.org/10.1210/jc.2008-0121
[122]  Trabados, S., Maione, L., Salenave, S., Baron, S., Gallarnd, F., Bry-Gauillard, H., Guiochon-Mantel, A., Chanson, P., Pitteloud, N., Sinisi, A.A., Brailly-Tabard, S. and Young, J. (2011) Estradiol Levels in Men with Congenial Hypogonadotropic Hypogonadism and the Effects of Different Modalities OF Different Treatment. Fertility and Sterility, 95, 2324- 2329.
http://dx.doi.org/10.1016/j.fertnstert.2011.03.091
[123]  Gennari, L., Nuti, R. and Bilezikian, J.P. (2004) Aromatase Activity and Bone Homeostasis in Men. Journal of Clinical Endocrinology & Metabolism, 89, 5898-5907.
http://dx.doi.org/10.1210/jc.2004-1717
[124]  Khosla, S., Amin, S. and Orwoll, E. (2008) Ostroporosis in Men. Endocrine Reviews, 29, 441-464.
http://dx.doi.org/10.1210/er.2008-0002
[125]  Khosla, S. (2010) Update in Male Osteoporosis Osteoporosis. Journal of Clinical Endocrinology & Metabolism, 95, 3-10.
http://dx.doi.org/10.1210/jc.2009-1740
[126]  Kochar Kaur, K., Allahbadia, G.N. and Singh, M. (2014) Male Hypogonadism-Areview of Secondary Hypogonadism with Special Emphasis on Hypogonadotropic Hypogonadism. Journal of Endocrinology, Diabetes & Obesity, 2, 1023.
[127]  Rochira, V., Zirilli, L., Maffei, L., Fremrou, V., Ananda, C., Baldi, M., Ghigo, E., Aomaretti, G., Carani, C. and Lanfranco, F. (2010) Tall Stature without Growth Hormone, Four Male Patients with Aromatase Deficiency. Journal of Clinical Endocrinology & Metabolism, 95, 1626-1633.
http://dx.doi.org/10.1210/jc.2009-1743
[128]  Pitteloud, N., Dwyer, A.A., DeCruz, S., Lee, H., Boepple, P.A., Crowley Jr., W.F. and Hayes, F.J. (2008) Inhibition of Luteinizing Hormone Secretion by Testosterone in Men Requires Aromatizarion for Its Pituitary but Not Its Hypothalamis Effects, Evidence from Tandem Study of Normal and Gonadotropin-Releasing Hormone Deficient Men. Journal of Clinical Endocrinology & Metabolism, 93, 784-791.
http://dx.doi.org/10.1210/jc.2007-2156
[129]  George, J.T., Veldhius, J.D., Roseweir, A.K., Newton, C.L., Fasccenda, E., Millar, R.P. and Anderson, R.A. (2011) Kisspeptin 10 Is a Potent Stimulator of LH & Increase Pulse Frequencty in Men. Journal of Clinical Endocrinology & Metabolism, 96, E1228-E1236.
http://dx.doi.org/10.1210/jc.2011-0089
[130]  Kochar Kaur, K., Allahbadia, G.N. and Singh, M. (2012) Kisspeptins in Human Reproduction-Future Therapeutic Potentials. Journal of Assisted Reproduction and Genetics, 29, 999-1011.
http://dx.doi.org/10.1007/s10815-012-9856-1
[131]  Jayasena, C.N., Comninos, A.N., DeSilva, A., Abbara, A., Veldhius, J.D., Nijher, J.M., Gniyu-Dada, Z., Vaal, M., Stamp, G., Ghatel, M.A., Bloom, S.R. and Dhillo, W.S. (2013) Effects of Neurokinin B Administration on Reproductive Hormone Secretion in Healthy Men and Women. Journal of Clinical Endocrinology & Metabolism, 99, E19-E27.
http://dx.doi.org/10.1210/jc.2012-2880
[132]  George, J.T. and Seminara, S.B. (2012) Kisspeptin and the Hypothamic Control of Reproduction, Lessons from the Human. Endocrinology, 153, 5130-5136.
http://dx.doi.org/10.1210/en.2012-1429
[133]  Young, J., George, J.T., Tello, J.A., Francou, B., Bouligard, J., Guiochon-Mauld, A., Brailly-Tabard, S., Anderson, R.A. and Millar, R.A. (2013) Kisspeptin Restores Pulsatile LH Secretion in Patients with NKB Signaling Deficiencies. Neuroendocrinology, 97, 193-202.
http://dx.doi.org/10.1159/000336376
[134]  Pingault, V., Bodereau, V., Baral, V., Marcos, S., Watanabe, Y., Chaout, A., Fouveaut, C., Leroy, C., Vener-Mine, O., Francannet, C., Dupin-Deguine, D., Hardelin, J.P., Dode, C. and Bondurand, N. (2013) Loss of Function Mutations in SOX10 Cause Kallmann Syndrome with Deafness. American Journal of Human Genetics, 92, 707-724.
http://dx.doi.org/10.1016/j.ajhg.2013.03.024
[135]  Jones, J. and Kemmann, E. (1976) Olfactory-Genital Dysplasia in the Female. Obstetrics & Gynecology Annual, 5, 443-446.
[136]  Casoni, F., Hutchins, I.B., Donohue, D., Fornaro, M., Condie, B.G. and Wray, S. (2012) SDF and GABA Interact to Regulate Aophilic Migration of GnRH Neurons. Journal of Cell Science, 125, 5015-5025.
http://dx.doi.org/10.1242/jcs.101675
[137]  Memi, F., Abe, P., Cariboni, A., Mackay, F., Parnavelas, J.G. and Stumin, R. (2013) CXC Chemokine Receptor 7 (CXCR7) Affects the Migration of GnRH Neurons by Regulating CXCL12 Availability. The Journal of Neuroscience, 33, 17527-17537.
http://dx.doi.org/10.1523/JNEUROSCI.0857-13.2013
[138]  Cariboni, A., Andrews, D.W., Memi, A.F., Ypsilanti, A.R., Zelina, P., Chedotal, A. and Parnavelas, J.G. (2012) Slit2 and Robo3 Modulate the Migration of GnRH Secreting Neurons. Development, 139, 3326-3327.
http://dx.doi.org/10.1242/dev.079418
[139]  Wray, S. (2010) From Nose to Brain, Development of Gonadotropin-Releasing Hormone-1 Neurons. Journal of Neuroendocrinology, 22, 743-753.
http://dx.doi.org/10.1111/j.1365-2826.2010.02034.x

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