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Brain Crosstalk in Puberty and Adolescence pp 155–162Cite as

Gonadotropic Axis Deficiency: A Neurodevelopmental Disorder

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Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI,volume 13))

Abstract

The onset of puberty remains a mysterious mechanism despite several recent major breakthroughs in the field of neuroendocrinology. Novel neuropeptides, along with new regulation networks of gene expression, have been described; however, the intimate molecular mechanisms defining the age of puberty onset have yet to be characterized. This article proposes to broaden the reflection surrounding the mechanisms that determine the onset of puberty as a developmental process, similar to those described for other neuronal networks. This new and original approach will bring further insight into the intricate interactions between the brain and the gonads that drive and maintain normal reproductive function.

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References

  • Ahmed EI, Zehr JL, Schulz KM, Lorenz BH, DonCarlos LL, Sisk CL (2008) Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions. Nat Neurosci 11:995–997

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Alazami AM, Al-Saif A, Al-Semari A, Bohlega S, Zlitni S, Alzahrani F, Bavi P, Kaya N, Colak D, Khalak H, Baltus A, Peterlin B, Danda S, Bhatia KP, Schneider SA, Sakati N, Walsh CA, Al-Mohanna F, Meyer B, Alkuraya FS (2008) Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome. Am J Hum Genet 83:684–691

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, Handley MT, Hadzhiev Y, Masood I, Straatman-Iwanowska AA, Cullinane AR, McNeill A, Pasha SS, Kirby GA, Foster K, Ahmed Z, Morton JE, Williams D, Graham JM, Dobyns WB, Burglen L, Ainsworth JR, Gissen P, Müller F, Maher ER, Barr FA, Aligianis IA (2011) Loss-of-function mutations in RAB18 cause Warburg micro syndrome. Am J Hum Genet 88:499–507

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bernard G, Chouery E, Putorti ML, Tetreault M, Takanohashi A, Carosso G, Clement I, Boespflug-Tanguy O, Rodriguez D, Delague V, Abou Ghoch J, Jalkh N, Dorboz I, Fribourg S, Teichmann M, Megarbane A, Schiffmann R, Vanderver A, Brais B (2011) Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet 89:415–423

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P, Lombes M, Millar RP, Guiochon-Mantel A, Young J (2009) Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. N Engl J Med 360:2742–2748

    Article  CAS  PubMed  Google Scholar 

  • de Roux N, Young J, Misrahi M, Schaison G, Milgrom E (1999) Loss of function mutations of the GnRH receptor: a new cause of hypogonadotropic hypogonadism. J Pediatr Endocrinol Metab 12(Suppl 1):267–275

    PubMed  Google Scholar 

  • de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100:10972–10976

    Article  PubMed Central  PubMed  Google Scholar 

  • Guimiot F, Chevrier L, Dreux S, Chevenne D, Caraty A, Delezoide AL, de Roux N (2012) Negative fetal FSH/LH regulation in late pregnancy is associated with declined kisspeptin/KISS1R expression in the tuberal hypothalamus. J Clin Endocrinol Metab 97:E2221–E2229

    Article  CAS  PubMed  Google Scholar 

  • Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, Carpanini SM, Borck G, Martorell L, Izzi C, Faravelli F, Accorsi P, Pinelli L, Basel-Vanagaite L, Peretz G, Abdel-Salam GM, Zaki MS, Jansen A, Mowat D, Glass I, Stewart H, Mancini G, Lederer D, Roscioli T, Giuliano F, Plomp AS, Rolfs A, Graham JM, Seemanova E, Poo P, García-Cazorla A, Edery P, Jackson IJ, Maher ER (2013) Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in Warburg micro syndrome and Martsolf syndrome. Hum Mutat 34:686–696

    Article  CAS  PubMed  Google Scholar 

  • Lomniczi A, Loche A, Castellano JM, Ronnekleiv OK, Bosch M, Kaidar G, Knoll JG, Wright H, Pfeifer GP, Ojeda SR (2013a) Epigenetic control of female puberty. Nat Neurosci 16:281–289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lomniczi A, Wright H, Castellano JM, Sonmez K, Ojeda SR (2013b) A system biology approach to identify regulatory pathways underlying the neuroendocrine control of female puberty in rats and nonhuman primates. Horm Behav 64:175–186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Margolin DH, Kousi M, Chan YM, Lim ET, Schmahmann JD, Hadjivassiliou M, Hall JE, Adam I, Dwyer A, Plummer L, Aldrin SV, O’Rourke J, Kirby A, Lage K, Milunsky A, Milunsky JM, Chan J, Hedley-Whyte ET, Daly MJ, Katsanis N, Seminara SB (2013) Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination. N Engl J Med 368:1992–2003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mitchell AL, Dwyer A, Pitteloud N, Quinton R (2011) Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol Metab 22:249–258

    CAS  PubMed  Google Scholar 

  • Nousbeck J, Spiegel R, Ishida-Yamamoto A, Indelman M, Shani-Adir A, Adir N, Lipkin E, Bercovici S, Geiger D, van Steensel MA, Steijlen PM, Bergman R, Bindereif A, Choder M, Shalev S, Sprecher E (2008) Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis. Am J Hum Genet 82:1114–1121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M (2012) Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev 92:1235–1316

    Article  CAS  PubMed  Google Scholar 

  • Pitteloud N, Durrani S, Raivio T, Sykiotis GP (2010) Complex genetics in idiopathic hypogonadotropic hypogonadism. Front Horm Res 39:142–153

    Article  CAS  PubMed  Google Scholar 

  • Prevot V, Bellefontaine N, Baroncini M, Sharif A, Hanchate NK, Parkash J, Campagne C, de Seranno S (2010) Gonadotrophin-releasing hormone nerve terminals, tanycytes and neurohaemal junction remodelling in the adult median eminence: functional consequences for reproduction and dynamic role of vascular endothelial cells. J Neuroendocrinol 22:639–649

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ramaswamy S, Dwarki K, Ali B, Gibbs RB, Plant TM (2013) The decline in pulsatile GnRH release, as reflected by circulating LH concentrations, during the infant-juvenile transition in the agonadal male rhesus monkey (Macaca mulatta) is associated with a reduction in kisspeptin content of KNDy neurons of the arcuate nucleus in the hypothalamus. Endocrinology 154:1845–1853

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sisk CL, Foster DL (2004) The neural basis of puberty and adolescence. Nat Neurosci 7:1040–1047

    Article  CAS  PubMed  Google Scholar 

  • Synofzik M, Gonzalez MA, Lourenco CM, Coutelier M, Haack TB, Rebelo A, Hannequin D, Strom TM, Prokisch H, Kernstock C et al (2014) PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Brain: J Neurol 137:69–77

    Article  Google Scholar 

  • Tâta B, Huijbregts L, Jacquier S, Csaba Z, Genin E, Meyer V, Leka S, Dupont J, Charles P, Chevenne D, Carel JC, Leger J, de Roux N (2014) Haploinsufficiency of Dmxl2, encoding a synaptic protein, causes infertility associated with a loss of GnRH neurons in mouse. PloS Biol 12(9):e1001952

    Google Scholar 

  • Tena-Sempere M (2012) Deciphering puberty: novel partners, novel mechanisms. Eur J Endocrinol 167:733–747

    Article  CAS  PubMed  Google Scholar 

  • Terasawa E, Guerriero KA, Plant TM (2013) Kisspeptin and puberty in mammals. Adv Exp Med Biol 784:253–273

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tetreault M, Choquet K, Orcesi S, Tonduti D, Balottin U, Teichmann M, Fribourg S, Schiffmann R, Brais B, Vanderver A, Bernard G (2011) Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. Am J Hum Genet 89:652–655

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN, Imamoglu S, Akalin NS, Yuksel B, O’Rahilly S, Semple RK (2009) TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet 41:354–358

    Article  CAS  PubMed  Google Scholar 

  • Topaloglu AK, Tello JA, Kota LD, Ozbek MN, Yilmaz MB, Erdogan S, Gurbuz F, Temiz F, Millar RP, Yuksel B (2012) Inactivating KISS1 mutation and hypogonadotropic hypogonadism. N Engl J Med 366:629–635

    Article  CAS  PubMed  Google Scholar 

  • Wierman ME, Kiseljak-Vassiliades K, Tobet S (2011) Gonadotropin-releasing hormone (GnRH) neuron migration: initiation, maintenance and cessation as critical steps to ensure normal reproductive function. Front Neuroendocrinol 32:43–52

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Inserm U1141, Univ Paris Diderot. Hôpital Robert Debré, 48 Boulevard Sérurier, 75019, Paris, France

    Lukas Huijbregts, Brooke Tata & Nicolas de Roux

Authors
  1. Lukas Huijbregts
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  2. Brooke Tata
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  3. Nicolas de Roux
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Corresponding author

Correspondence to Nicolas de Roux .

Editor information

Editors and Affiliations

  1. Developmental Neuroendocrinology Unit, G GIGA Neurosciences, University of Liège, Liège, Belgium

    Jean-Pierre Bourguignon

  2. Serv. d'endocrinologie diabetol. pédiatr, Hopital Robert Debre, Paris, Paris, France

    Jean-Claude Carel

  3. Fondation Ipsen, Boulogne-Billancourt, France

    Yves Christen

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© 2015 Springer International Publishing Switzerland

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Huijbregts, L., Tata, B., de Roux, N. (2015). Gonadotropic Axis Deficiency: A Neurodevelopmental Disorder. In: Bourguignon, JP., Carel, JC., Christen, Y. (eds) Brain Crosstalk in Puberty and Adolescence. Research and Perspectives in Endocrine Interactions, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-09168-6_11

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