title: Hypothalamic control of the male neonatal testosterone surge.
abstract: Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin-GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse.
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand jenny.clarkson@otago.ac.nz.
authors.forename: Jenny
authors.initials: J
authors.lastname: Clarkson
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Allan E
authors.initials: AE
authors.lastname: Herbison
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone
keywords: GPR54; GnRH; kisspeptin; sexual differentiation; testosterone
references.citation: N Engl J Med. 2003 Oct 23;349(17):1614-27
references.pmid: 14573733
references.citation: Biol Reprod. 2009 Dec;81(6):1216-25
references.pmid: 19684332
references.citation: Endocrinology. 2007 Apr;148(4):1774-83
references.pmid: 17204549
references.citation: Nat Commun. 2013;4:2492
references.pmid: 24051579
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14077-82
references.pmid: 9391155
references.citation: Am J Primatol. 1987;13(1):37-49
references.pmid: 31973484
references.citation: Endocrinology. 1980 Jan;106(1):306-16
references.pmid: 7349961
references.citation: Arch Int Physiol Biochim Biophys. 1992 Mar-Apr;100(2):127-31
references.pmid: 1379488
references.citation: FEBS Lett. 1976 Sep 15;68(1):19-22
references.pmid: 183986
references.citation: Horm Behav. 1993 Jun;27(2):216-30
references.pmid: 8349280
references.citation: Endocrinology. 1998 Mar;139(3):1141-6
references.pmid: 9492048
references.citation: Biochem Biophys Res Commun. 2003 Dec 26;312(4):1357-63
references.pmid: 14652023
references.citation: J Neurosci. 2007 Aug 15;27(33):8826-35
references.pmid: 17699664
references.citation: Biol Reprod. 1992 Oct;47(4):561-7
references.pmid: 1391342
references.citation: J Neurosci. 2014 Mar 5;34(10):3756-66
references.pmid: 24599473
references.citation: J Endocrinol. 1994 Jun;141(3):439-47
references.pmid: 8071642
references.citation: J Clin Endocrinol Metab. 1975 Nov;41(5):977-80
references.pmid: 1184729
references.citation: Sex Med. 2015 Mar;3(1):32-41
references.pmid: 25844173
references.citation: Endocrinology. 1972 Apr;90(4):1025-31
references.pmid: 5011044
references.citation: Endocrinology. 2006 Dec;147(12):5817-25
references.pmid: 16959837
references.citation: J Neuroendocrinol. 2012 Jun;24(6):907-15
references.pmid: 22340076
references.citation: Pediatr Res. 1992 Nov;32(5):605-7
references.pmid: 1480465
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13666-71
references.pmid: 15342910
references.citation: J Endocrinol. 1976 Jun;69(3):381-4
references.pmid: 950526
references.citation: Endocrinology. 2005 Jul;146(7):2976-84
references.pmid: 15831567
references.citation: Endocrinology. 2010 Mar;151(3):1142-52
references.pmid: 20068010
references.citation: Endocrinology. 2002 Nov;143(11):4477-82
references.pmid: 12399445
references.citation: J Endocrinol. 1980 Oct;87(1):81-7
references.pmid: 7430918
references.citation: Eur J Endocrinol. 1995 Sep;133(3):366-74
references.pmid: 7581956
references.citation: Dev Growth Differ. 2011 Feb;53(2):236-44
references.pmid: 21338349
references.citation: Nat Neurosci. 2004 Jun;7(6):643-50
references.pmid: 15156148
references.citation: Endocrinology. 2013 Sep;154(9):3273-83
references.pmid: 23825121
references.citation: J Neuroendocrinol. 2012 Oct;24(10):1284-95
references.pmid: 22530935
references.citation: Front Endocrinol (Lausanne). 2014 Feb 21;5:15
references.pmid: 24600437
references.citation: Horm Behav. 1995 Sep;29(3):322-37
references.pmid: 7490008
references.citation: Nat Rev Endocrinol. 2011 Oct 18;8(3):172-82
references.pmid: 22009162
references.citation: Endocrinology. 2009 Sep;150(9):4241-7
references.pmid: 19497973
references.citation: Endocrinology. 2012 Nov;153(11):5384-93
references.pmid: 22989626
references.citation: Horm Behav. 1990 Dec;24(4):470-83
references.pmid: 2286363
references.citation: Annu Rev Neurosci. 2002;25:507-36
references.pmid: 12052919
references.citation: PLoS One. 2010 Jul 30;5(7):e11911
references.pmid: 20689830
references.citation: Recent Prog Horm Res. 1976;32:161-243
references.pmid: 785555
references.citation: J Neurosci. 2012 Feb 15;32(7):2241-7
references.pmid: 22396398
references.citation: J Neuroendocrinol. 2002 Nov;14(11):904-10
references.pmid: 12421344
references.citation: Biol Reprod. 2012 Dec 06;87(6):129
references.pmid: 23034157
references.citation: Endocrinology. 1983 Dec;113(6):2216-20
references.pmid: 6641633
references.citation: J Neurosci. 2014 Nov 12;34(46):15297-305
references.pmid: 25392497
references.citation: Front Neuroendocrinol. 2008 Jan;29(1):1-16
references.pmid: 17720235
references.citation: Int J Dev Neurosci. 1983;1(3):187-90
references.pmid: 24875849
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9
references.pmid: 17563351
references.citation: Endocrinology. 2008 Feb;149(2):597-604
references.pmid: 18006629
references.citation: Endocrinology. 2005 Sep;146(9):3686-92
references.pmid: 15919741
references.citation: Front Endocrinol (Lausanne). 2013 Oct 11;4:140
references.pmid: 24130552
references.citation: Mol Cell Endocrinol. 2009 Jul 10;306(1-2):2-8
references.pmid: 19059463
references.citation: Curr Opin Neurobiol. 2010 Dec;20(6):776-83
references.pmid: 20934320
references.citation: Endocrinology. 1985 Apr;116(4):1341-50
references.pmid: 3971918
references.citation: Reprod Biol Endocrinol. 2005 Sep 21;3:48
references.pmid: 16176578
references.citation: Endocrinology. 2009 Jul;150(7):3214-20
references.pmid: 19299459
references.citation: Endocrinology. 1984 May;114(5):1754-60
references.pmid: 6714163
references.citation: Front Neuroendocrinol. 1993 Jul;14(3):173-213
references.pmid: 8349003
references.citation: Nature. 2014 May 15;509(7500):282-3
references.pmid: 24834516
references.citation: Experientia. 1976 Oct 15;32(10):1347-8
references.pmid: 61893
references.citation: Endocrinology. 2009 Mar;150(3):1400-12
references.pmid: 18948403
references.citation: Physiol Rev. 2008 Jan;88(1):91-124
references.pmid: 18195084
references.citation: Nat Neurosci. 2011 Jun;14(6):677-83
references.pmid: 21613996
references.citation: J Clin Endocrinol Metab. 1993 May;76(5):1319-24
references.pmid: 8496324
references.citation: J Comp Neurol. 2006 Mar 1;495(1):122-32
references.pmid: 16432907
references.citation: Brain Res. 1996 Sep 23;734(1-2):10-8
references.pmid: 8896803
references.citation: Endocrinology. 2012 Feb;153(2):782-93
references.pmid: 22202164
references.citation: Horm Behav. 1999 Apr;35(2):186-94
references.pmid: 10202126
references.citation: Endocrinology. 1959 Sep;65:369-82
references.pmid: 14432658
references.citation: Endocrinology. 2004 Mar;145(3):1453-63
references.pmid: 14645113
references.citation: Endocrinology. 2015 Sep;156(9):3084-90
references.pmid: 26172029
references.citation: Dev Biol. 2004 Jun 1;270(1):1-18
references.pmid: 15136137
references.citation: J Clin Endocrinol Metab. 1990 Nov;71(5):1344-8
references.pmid: 2229291
references.citation: J Endocrinol. 1979 Jan;80(1):103-10
references.pmid: 429945
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16372-7
references.pmid: 20805495
references.citation: Eur J Neurosci. 2010 Dec;32(12):2096-104
references.pmid: 21143664
references.citation: Prog Brain Res. 2010;186:3-12
references.pmid: 21094882
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10972-6
references.pmid: 12944565
references.citation: Acta Endocrinol (Copenh). 1976 Sep;83(1):158-65
references.pmid: 183442
references.citation: Front Neurosci. 2012 Feb 21;6:26
references.pmid: 22363256
references.citation: J Neuroendocrinol. 2010 Oct;22(10):1113-25
references.pmid: 20722977
references.citation: Endocrinology. 1978 Dec;103(6):1985-91
references.pmid: 748030
references.citation: Brain Res Dev Brain Res. 1988 Dec 1;44(2):314-8
references.pmid: 3224432
references.citation: Endocrinology. 2010 Jan;151(1):312-21
references.pmid: 19966188