title: Location, location, location: genetic regulation of neural sex differences.
abstract: Sex differences in many behaviors such as cognition, mood, and motor skills are well-documented in animals and humans and are regulated by many neural circuits. Sexual dimorphisms within cell populations in these circuits play critical roles in the production of these behavioral dichotomies. Here we focus on three proteins that have well described sexual dimorphisms; calbindin-D28k, a calcium binding protein, tyrosine hydroxylase, the rate limiting enzyme involved in dopamine synthesis and vasopressin, a neuropeptide with central and peripheral sites of action. We describe the sex differences in subpopulations of these proteins, with particular emphasis on laboratory mice. Our thrust is to examine genetic bases of sex differences and how the use of genetically modified models has advanced our understanding of this topic. Regional sex differences in the expression of these three proteins are driven by sex chromosome complement, steroid receptors or in some instances both. While studies of sex differences attributable to sex chromosome genes are still few in number it is exciting to note that this variable factors into expression differences for all three of these proteins. Different genetic mechanisms, which elaborate sex differences, may be employed stochastically in different cell populations. Alternately, general patterns involving the timing of differentiation of the sex differences, relative to the "critical period" in hormonal differences between males and female neonates may emerge. In conclusion, future directions in this area should include examination of the importance of location, timing, steroidal receptor/sex chromosome gene synergy and epigenetics in molding neural sex differences.
authors: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA. jma6n@virginia.edu
authors: Jean LeBeau
authors: JL
authors: Abel
authors: Emilie F
authors: EF
authors: Rissman
references: Brain Res Dev Brain Res. 1996 May 31;93(1-2):136-42
references: 8804700
references: Int J Dev Neurosci. 2008 May-Jun;26(3-4):259-68
references: 18367364
references: Trends Neurosci. 1998 Sep;21(9):375-82
references: 9735945
references: Nat Struct Mol Biol. 2006 Jul;13(7):641-7
references: 16799559
references: Horm Behav. 1979 Dec;13(3):207-13
references: 552369
references: Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):8028-33
references: 8755597
references: Brain Res Dev Brain Res. 1996 Oct 23;96(1-2):281-4
references: 8922690
references: J Comp Neurol. 1982 Dec 1;212(2):118-30
references: 7187914
references: J Neurobiol. 1997 Nov;33(5):572-84
references: 9369460
references: Trends Neurosci. 1991 Oct;14(10):468-73
references: 1722367
references: Prog Brain Res. 1998;119:483-99
references: 10074808
references: Mol Endocrinol. 1995 Mar;9(3):319-26
references: 7776978
references: Neuroscience. 2006;138(3):929-38
references: 16310316
references: J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):375-80
references: 9365213
references: Nat Neurosci. 2006 Feb;9(2):220-6
references: 16388309
references: Neuroreport. 1996 Apr 26;7(6):1224-8
references: 8817537
references: Chronobiol Int. 2010 Jan;27(1):68-82
references: 20205558
references: Med Biol. 1976 Dec;54(6):427-53
references: 12423
references: J Neuroendocrinol. 2008 Jun;20(6):880-4
references: 18601712
references: Endocrinology. 2010 May;151(5):2297-305
references: 20237133
references: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13666-71
references: 15342910
references: Science. 1980 May 9;208(4444):597-9
references: 7367881
references: Epigenetics. 2009 Jan;4(1):47-53
references: 19029819
references: Endocrinology. 1966 May;78(5):1053-60
references: 5935501
references: Neurosci Lett. 1989 Jul 31;102(2-3):185-90
references: 2812498
references: J Steroid Biochem. 1988 Sep;31(3):283-6
references: 3419158
references: Front Neuroendocrinol. 2009 Oct;30(4):429-441
references: 19520105
references: Neuroscientist. 2009 Dec;15(6):599-610
references: 19700741
references: J Neurosci. 2006 Feb 22;26(8):2335-42
references: 16495461
references: Anat Embryol (Berl). 1987;177(1):15-28
references: 3439634
references: Science. 1971 Aug 20;173(3998):731-3
references: 5568506
references: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1488-93
references: 9037080
references: J Neurobiol. 2003 Feb 15;54(3):502-10
references: 12532400
references: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16692-7
references: 19805359
references: J Neurosci. 2009 Aug 5;29(31):9714-8
references: 19657024
references: Brain Res. 1985 Mar 18;330(1):55-64
references: 2859086
references: J Endocrinol. 1984 Jan;100(1):7-11
references: 6690645
references: Horm Behav. 1977 Dec;9(3):249-63
references: 611076
references: J Neuroendocrinol. 2000 May;12(5):397-402
references: 10792577
references: J Comp Neurol. 1997 Jul 21;384(1):142-64
references: 9214545
references: Acta Neurochir Suppl (Wien). 1990;47:90-4
references: 2407061
references: Mol Neurobiol. 2008 Apr-Jun;37(2-3):116-25
references: 18521763
references: Peptides. 1989 May-Jun;10(3):615-9
references: 2780420
references: Neurosci Biobehav Rev. 1983 Summer;7(2):263-80
references: 6348607
references: J Neurosci. 1991 May;11(5):1325-33
references: 1674002
references: Biol Reprod. 2009 Nov;81(5):956-65
references: 19605792
references: Dev Neurobiol. 2007 Sep 1;67(10):1371-81
references: 17638388
references: Neurosci Lett. 1993 Mar 5;151(1):41-4
references: 8469435
references: Endocrinology. 2005 Mar;146(3):1559-67
references: 15591140
references: Neuropharmacology. 2002 Mar;42(4):444-58
references: 11955516
references: Mol Cell. 2004 Jun 18;14(6):727-38
references: 15200951
references: Acta Physiol Pol. 1977;28(15):77-91
references: 556573
references: J Neurobiol. 2000 Feb 15;42(3):315-22
references: 10645971
references: Eur J Neurosci. 1996 Aug;8(8):1718-24
references: 8921262
references: Neurosci Res. 1998 Sep;32(1):97-101
references: 9831256
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14077-82
references: 9391155
references: Genes Brain Behav. 2004 Feb;3(1):20-6
references: 14960012
references: Endocrinology. 1965 Feb;76:226-39
references: 14262651
references: Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R824-30
references: 19052319
references: Horm Behav. 2009 May;55(5):605-10
references: 19446077
references: Int J Dev Neurosci. 1989;7(6):603-11
references: 2603757
references: Brain Res. 1982 May 13;239(2):519-25
references: 7093699
references: Brain Res. 1988 Aug 2;457(1):143-7
references: 3167559
references: J Neurosci. 2008 Apr 23;28(17):4521-7
references: 18434530
references: Front Behav Neurosci. 2010 Mar 30;4:12
references: 20407578
references: Brain Res Dev Brain Res. 1999 Jun 2;115(2):171-82
references: 10407134
references: PLoS One. 2008 Jul 02;3(7):e2553
references: 18596936
references: Cerebellum. 2008;7(1):38-47
references: 18418672
references: Endocrinology. 2008 Aug;149(8):4142-50
references: 18467440
references: Brain Res Mol Brain Res. 1989 Dec;6(4):297-310
references: 2574404
references: Front Neuroendocrinol. 2009 Jan;30(1):1-9
references: 19028515
references: Nat Neurosci. 2002 Oct;5(10):933-4
references: 12244322
references: Brain Res Mol Brain Res. 1990 Oct;8(4):283-90
references: 2176707
references: Kidney Int. 2009 Nov;76(10):1035-9
references: 19693000
references: Brain Res. 1973 May 17;54:1-29
references: 4122682
references: Endocrinology. 1963 Aug;73:210-6
references: 14076200
references: Brain Res Dev Brain Res. 2005 Jun 9;157(1):34-41
references: 15939083
references: J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):85-96
references: 10418982
references: Horm Behav. 2001 Aug;40(1):51-64
references: 11467884
references: J Comp Neurol. 1969 Jul;136(3):269-93
references: 5788129
references: FASEB J. 2010 Jan;24(1):184-95
references: 19752176
references: Endocrinology. 1993 Aug;133(2):433-9
references: 8344188
references: Prog Brain Res. 1983;60:115-22
references: 6665132
references: Cerebellum. 2003;2(4):242-62
references: 14964684
references: Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):122-32
references: 10095084
references: Dev Neurobiol. 2008 Jun;68(7):981-95
references: 18418875
references: Neuroendocrinology. 1985 Jun;40(6):501-10
references: 2861581
references: Endocrinology. 1959 Sep;65:369-82
references: 14432658
references: Endocrinology. 2000 Nov;141(11):4056-64
references: 11089536
references: Horm Behav. 1997 Apr;31(2):136-44
references: 9154434
references: Brain Res. 1996 Sep 23;734(1-2):10-8
references: 8896803
references: J Neurosci. 2003 Apr 15;23(8):3469-77
references: 12716955
references: Horm Behav. 1994 Dec;28(4):313-9
references: 7729800
references: Behav Brain Res. 2007 Mar 28;178(2):250-61
references: 17275105
references: J Neuroendocrinol. 2008 Oct;20(10):1155-64
references: 18680559
references: Ann N Y Acad Sci. 1992 Jun 12;652:227-42
references: 1626831
references: Open Neuroendocrinol J. 2009;2:20-30
references: 20396406
references: Biochem Biophys Res Commun. 2008 Jun 20;371(1):127-31
references: 18413141
references: Horm Behav. 2008 Jun;54(1):98-106
references: 18346740
references: Brain Res Mol Brain Res. 1999 Nov 10;73(1-2):60-7
references: 10581398
references: Curr Biol. 2006 Feb 21;16(4):415-20
references: 16488877
references: Neurosci Biobehav Rev. 2003 Sep;27(4):385-99
references: 12946691
references: J Neurosci. 2003 Mar 15;23(6):2357-62
references: 12657695
references: Cell Mol Life Sci. 2009 Jan;66(2):275-300
references: 19099190
references: Prog Brain Res. 1978;48:149-70
references: 746152
references: Endocrinology. 1964 Oct;75:627-48
references: 14211911
references: Epigenetics. 2010 Apr;5(3):194-9
references: 20339319
references: Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7953-7
references: 1518820
references: Horm Behav. 2001 Jun;39(4):285-94
references: 11374914
references: Annu Rev Neurosci. 1997;20:245-67
references: 9056714
references: Prog Brain Res. 2008;170:17-27
references: 18655868
references: Hum Mol Genet. 1998 Apr;7(4):715-27
references: 9499427
references: J Neuroendocrinol. 2002 Dec;14(12):971-8
references: 12472878
references: J Comp Neurol. 2010 Sep 1;518(17):3618-29
references: 20593361
references: Neuroscience. 2008 Jun 26;154(3):911-21
references: 18514427
references: Neuroendocrinology. 2011;93(4):230-40
references: 21325792
references: Brain Res. 1978 Jun 16;148(2):333-46
references: 656937
references: J Neurobiol. 1999 Nov 5;41(2):252-66
references: 10512982
references: J Nutr. 2010 Jun;140(6):1072-9
references: 20357080
references: Eur J Neurosci. 2009 Feb;29(4):768-76
references: 19250439
references: Med Biol. 1977 Feb;55(1):21-40
references: 15169
references: Brain Res. 1985 Jan 28;325(1-2):391-4
references: 3978433
references: J Neurosci. 2002 Oct 15;22(20):9005-14
references: 12388607