title: Sexual differentiation and development of forebrain reproductive circuits.
abstract: Males and females exhibit numerous anatomical and physiological differences in the brain that often underlie important sex differences in physiology or behavior, including aspects relating to reproduction. Neural sex differences are both region-specific and trait-specific and may consist of divergences in synapse morphology, neuron size and number, and specific gene expression levels. In most cases, sex differences are induced by the sex steroid hormonal milieu during early perinatal development. In rodents, the hypothalamic anteroventral periventricular nucleus (AVPV) is sexually differentiated as a result of postnatal sex steroids, and also specific neuronal populations in this nucleus are sexually dimorphic, with females possessing more kisspeptin, dopaminergic, and GABA/glutamate neurons than males. The ability of female rodents, but not males, to display an estrogen-induced luteinizing hormone (LH) surge is consistent with the higher levels of these neuropeptides in the AVPV of females. Of these AVPV populations, the recently identified kisspeptin system has been most strongly implicated as a crucial component of the sexually dimorphic LH surge mechanism, though GABA and glutamate have also received some attention. New findings have suggested that the sexual differentiation and development of kisspeptin neurons in the AVPV is mediated by developmental estradiol signaling. Although apoptosis is the most common process implicated in neuronal sexual differentiation, it is currently unknown how developmental estradiol acts to differentiate specific neuronal populations in the AVPV, such as kisspeptin or dopaminergic neurons.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Semaan
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kauffman
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D009415:Nerve Net / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology*; D013256:Steroids / Q000494:pharmacology
chemical_list: D013256:Steroids
references.citation: Endocrinology. 2006 Dec;147(12):5817-25
references.pmid: 16959837
references.citation: Biol Reprod. 2009 Dec;81(6):1216-25
references.pmid: 19684332
references.citation: Horm Behav. 2009 May;55(5):570-8
references.pmid: 19446073
references.citation: Horm Behav. 2009 May;55(5):589-96
references.pmid: 19446075
references.citation: Obstet Gynecol Surv. 2008 Mar;63(3):189-94
references.pmid: 18279545
references.citation: Am J Physiol Endocrinol Metab. 2009 Nov;297(5):E1212-21
references.pmid: 19755669
references.citation: Neurotoxicology. 2008 Nov;29(6):988-97
references.pmid: 18656497
references.citation: Dev Neurobiol. 2007 Feb 15;67(3):355-62
references.pmid: 17443793
references.citation: Neuroscience. 2009 Feb 18;158(4):1251-6
references.pmid: 19059313
references.citation: Nat Rev Neurosci. 2010 Jan;11(1):9-17
references.pmid: 20019686
references.citation: N Engl J Med. 2003 Oct 23;349(17):1614-27
references.pmid: 14573733
references.citation: J Neurosci. 2004 Sep 15;24(37):8097-105
references.pmid: 15371511
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: J Neurosci. 2008 Aug 27;28(35):8691-7
references.pmid: 18753370
references.citation: Brain Res Rev. 2008 Mar;57(2):277-87
references.pmid: 17604108
references.citation: Behav Brain Res. 1998 May;92(2):195-203
references.pmid: 9638961
references.citation: J Comp Neurol. 1982 Dec 1;212(2):118-30
references.pmid: 7187914
references.citation: Neuroscience. 2006;138(3):947-55
references.pmid: 16310321
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1761-6
references.pmid: 15665093
references.citation: Endocrinology. 2010 Feb;151(2):722-30
references.pmid: 19952274
references.citation: Mol Cell Endocrinol. 2010 Aug 5;324(1-2):51-63
references.pmid: 20083160
references.citation: J Biol Chem. 2001 Sep 14;276(37):34631-6
references.pmid: 11457843
references.citation: Eur J Pharmacol. 2003 Feb 28;463(1-3):199-216
references.pmid: 12600711
references.citation: J Neurosci. 2009 Oct 14;29(41):12815-23
references.pmid: 19828794
references.citation: J Obstet Gynecol Neonatal Nurs. 2007 May-Jun;36(3):263-74
references.pmid: 17489932
references.citation: Endocrinology. 2010 May;151(5):2297-305
references.pmid: 20237133
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13666-71
references.pmid: 15342910
references.citation: Mol Endocrinol. 2002 Dec;16(12):2872-91
references.pmid: 12456806
references.citation: J Neurosci. 2005 Dec 7;25(49):11349-56
references.pmid: 16339030
references.citation: Oncogene. 2007 Feb 26;26(9):1324-37
references.pmid: 17322918
references.citation: J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):325-9
references.pmid: 7626474
references.citation: Endocrinology. 2009 Sep;150(9):4241-7
references.pmid: 19497973
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16692-7
references.pmid: 19805359
references.citation: Neuroendocrinology. 2004;80(4):264-72
references.pmid: 15665556
references.citation: Annu Rev Neurosci. 2002;25:507-36
references.pmid: 12052919
references.citation: J Neurosci. 2009 Aug 5;29(31):9714-8
references.pmid: 19657024
references.citation: Brain Res. 1985 Mar 18;330(1):55-64
references.pmid: 2859086
references.citation: Endocrinology. 2005 Apr;146(4):1689-97
references.pmid: 15637288
references.citation: Endocrinology. 2007 Apr;148(4):1774-83
references.pmid: 17204549
references.citation: J Neuroendocrinol. 2009 Mar;21(4):305-11
references.pmid: 19207812
references.citation: Endocrinology. 2004 Feb;145(2):495-9
references.pmid: 14617578
references.citation: J Reprod Dev. 2007 Apr;53(2):367-78
references.pmid: 17213691
references.citation: Front Neuroendocrinol. 1998 Oct;19(4):323-62
references.pmid: 9799588
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14077-82
references.pmid: 9391155
references.citation: Cell. 2007 Feb 23;128(4):635-8
references.pmid: 17320500
references.citation: Endocrinology. 2009 Aug;150(8):3664-71
references.pmid: 19443569
references.citation: Endocrinology. 2008 Sep;149(9):4632-7
references.pmid: 18499746
references.citation: Trends Neurosci. 2007 Oct;30(10):504-11
references.pmid: 17904653
references.citation: Reproduction. 2006 Apr;131(4):623-30
references.pmid: 16595713
references.citation: Nature. 2001 May 31;411(6837):613-7
references.pmid: 11385580
references.citation: Neuroendocrinology. 1985 Jun;40(6):501-10
references.pmid: 2861581
references.citation: Eur J Neurosci. 2008 Feb;27(4):791-800
references.pmid: 18333959
references.citation: Endocrinology. 2005 Jan;146(1):156-63
references.pmid: 15375028
references.citation: Brain Res. 1992 May 8;579(2):321-6
references.pmid: 1352729
references.citation: Peptides. 2009 Jan;30(1):83-93
references.pmid: 18644414
references.citation: J Neurosci. 2006 Jun 21;26(25):6687-94
references.pmid: 16793876
references.citation: J Neuroendocrinol. 2009 Mar;21(4):393-9
references.pmid: 19207822
references.citation: J Neurobiol. 2006 Nov;66(13):1411-9
references.pmid: 17013925
references.citation: J Neurosci. 1998 Apr 15;18(8):3003-13
references.pmid: 9526017
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10972-6
references.pmid: 12944565
references.citation: Physiol Behav. 2004 Nov 15;83(2):217-32
references.pmid: 15488541
references.citation: Nat Neurosci. 2004 Oct;7(10):1034-9
references.pmid: 15452574
references.citation: J Biol Chem. 2001 Aug 3;276(31):28969-75
references.pmid: 11387329
references.citation: Endocrinology. 1971 Jul;89(1):112-5
references.pmid: 5089656