title: Estrogen signaling in hypothalamic circuits controlling reproduction.
abstract: It is well known that many of the actions of 17β-estradiol (E2) in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there is compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. Yet, it is not well understood how estrogen signals via membrane receptors and how these signals impact not only membrane excitability but also gene transcription in neurons that modulate GnRH neuronal excitability. Indeed, it has been known for some time that E2 can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, E2 can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review will consider our current knowledge of rapid membrane-initiated and intracellular signaling by E2 in hypothalamic neurons critical for reproductive function.
authors.affiliation: Department of Physiology and Pharmacology, Portland, OR 97239, USA. kellym@ohsu.edu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Kelly
authors.forename: Jian
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000818:Animals; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D054411:Receptors, Leptin / Q000502:physiology; D012098:Reproduction / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D017470:Receptors, Glutamate; D054411:Receptors, Leptin; D004958:Estradiol; D017526:Receptor, IGF Type 1
references.citation: Brain Res. 1998 Apr 27;791(1-2):341-6
references.pmid: 9593984
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2537-42
references.pmid: 15699332
references.citation: Nat Rev Mol Cell Biol. 2004 Dec;5(12):959-70
references.pmid: 15573134
references.citation: Brain Res Mol Brain Res. 2002 Oct 30;107(1):80-8
references.pmid: 12414126
references.citation: J Neurosci. 1994 Oct;14(10):6196-204
references.pmid: 7931572
references.citation: J Comp Neurol. 1998 Jun 15;395(4):535-47
references.pmid: 9619505
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4661-6
references.pmid: 15070774
references.citation: Mol Cell. 2010 Feb 26;37(4):541-50
references.pmid: 20188672
references.citation: J Neuroendocrinol. 2006 Apr;18(4):298-303
references.pmid: 16503925
references.citation: J Biol Chem. 1998 Feb 20;273(8):4465-9
references.pmid: 9468499
references.citation: Cardiovasc Res. 2007 Mar 1;73(4):641-7
references.pmid: 17137569
references.citation: J Neurosci. 2006 May 24;26(21):5649-55
references.pmid: 16723521
references.citation: Neuroendocrinology. 1996 Aug;64(2):114-23
references.pmid: 8857605
references.citation: Endocrinology. 2004 Mar;145(3):1069-74
references.pmid: 14670986
references.citation: J Neurosci. 2009 Jul 22;29(29):9390-5
references.pmid: 19625529
references.citation: NIDA Res Monogr. 1986;71:81-8
references.pmid: 2432429
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13391-5
references.pmid: 11687663
references.citation: Endocrinology. 1999 Feb;140(2):660-6
references.pmid: 9927291
references.citation: Steroids. 2008 Oct;73(9-10):985-91
references.pmid: 18342349
references.citation: J Biol Chem. 1997 Dec 19;272(51):32686-95
references.pmid: 9405487
references.citation: J Neurosci. 2001 Mar 15;21(6):2085-93
references.pmid: 11245692
references.citation: Trends Neurosci. 1988 Jul;11(7):308-14
references.pmid: 2465635
references.citation: Mol Endocrinol. 1999 Feb;13(2):307-19
references.pmid: 9973260
references.citation: Neurochem Res. 2004 Jun;29(6):1189-200
references.pmid: 15176476
references.citation: Nature. 1998 Feb 19;391(6669):803-6
references.pmid: 9486652
references.citation: Brain Res Mol Brain Res. 2003 Apr 10;112(1-2):170-6
references.pmid: 12670715
references.citation: Endocrinology. 1995 May;136(5):2341-4
references.pmid: 7720682
references.citation: Science. 1986 Mar 7;231(4742):1150-4
references.pmid: 3753802
references.citation: Endocrinology. 2003 Sep;144(9):3828-35
references.pmid: 12933654
references.citation: Hum Reprod. 1993 Nov;8 Suppl 2:151-3
references.pmid: 8276950
references.citation: J Comp Neurol. 1994 Mar 1;341(1):68-77
references.pmid: 8006224
references.citation: Brain Res Bull. 1984 Apr;12(4):399-407
references.pmid: 6203621
references.citation: Mol Endocrinol. 2000 Jul;14(7):1086-98
references.pmid: 10894157
references.citation: Recent Prog Horm Res. 2004;59:287-304
references.pmid: 14749507
references.citation: Mol Endocrinol. 1994 Jan;8(1):5-11
references.pmid: 8152430
references.citation: J Neurosci. 2002 Mar 15;22(6):2401-8
references.pmid: 11896179
references.citation: Diabetes. 2004 Dec;53(12):3067-73
references.pmid: 15561935
references.citation: Fed Proc. 1978 Feb;37(2):115-20
references.pmid: 203488
references.citation: Neuron. 2004 Jun 24;42(6):983-91
references.pmid: 15207242
references.citation: J Neurosci. 2003 Jul 2;23(13):5771-7
references.pmid: 12843281
references.citation: Cell. 1993 Sep 10;74(5):919-28
references.pmid: 8374957
references.citation: J Clin Invest. 2008 May;118(5):1796-805
references.pmid: 18382766
references.citation: Nat Med. 2007 Jan;13(1):89-94
references.pmid: 17195839
references.citation: J Neurosci. 1998 Jan 1;18(1):559-72
references.pmid: 9412531
references.citation: J Neurosci. 2007 Sep 12;27(37):9941-50
references.pmid: 17855608
references.citation: J Neurosci. 2009 Aug 26;29(34):10552-62
references.pmid: 19710308
references.citation: J Clin Endocrinol Metab. 1988 Oct;67(4):695-700
references.pmid: 3138276
references.citation: J Steroid Biochem. 1988;30(1-6):263-6
references.pmid: 3386250
references.citation: J Neurosci Res. 2002 Dec 15;70(6):799-807
references.pmid: 12444602
references.citation: Steroids. 2005 May-Jun;70(5-7):397-406
references.pmid: 15862823
references.citation: Nat Cell Biol. 1999 Jul;1(3):183-8
references.pmid: 10559906
references.citation: Sci STKE. 2002 Jun 25;2002(138):re9
references.pmid: 12084906
references.citation: Endocrinology. 2008 Dec;149(12):5934-42
references.pmid: 18653714
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12267-71
references.pmid: 11572951
references.citation: Brain Res. 1976 Sep 10;114(1):152-7
references.pmid: 986858
references.citation: Mol Cell Endocrinol. 2003 Aug 29;206(1-2):13-22
references.pmid: 12943986
references.citation: J Neurosci. 2007 Sep 19;27(38):10153-64
references.pmid: 17881521
references.citation: J Neurosci. 2006 Apr 12;26(15):4104-10
references.pmid: 16611827
references.citation: Gene. 2003 Nov 27;320:3-21
references.pmid: 14597384
references.citation: J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):187-93
references.pmid: 12650715
references.citation: Front Neuroendocrinol. 2005 Sep;26(2):65-84
references.pmid: 16009409
references.citation: Mol Pharmacol. 2000 Dec;58(6):1570-80
references.pmid: 11093798
references.citation: Neuroendocrinology. 1993 May;57(5):789-800
references.pmid: 8413816
references.citation: J Neurosci. 2010 Jan 27;30(4):1560-5
references.pmid: 20107083
references.citation: Mol Pharmacol. 1997 Apr;51(4):605-12
references.pmid: 9106625
references.citation: Horm Behav. 2001 Sep;40(2):169-77
references.pmid: 11534978
references.citation: Neuroendocrinology. 1995 Jun;61(6):695-703
references.pmid: 7544880
references.citation: J Neurosci. 2006 Oct 25;26(43):11072-82
references.pmid: 17065449
references.citation: J Neurosci. 2009 Dec 2;29(48):15323-30
references.pmid: 19955385
references.citation: J Neurosci. 2004 Jan 28;24(4):947-55
references.pmid: 14749439
references.citation: J Comp Neurol. 2008 Feb 20;506(6):895-911
references.pmid: 18085586
references.citation: J Neurosci. 1990 Nov;10(11):3627-34
references.pmid: 1977895
references.citation: Clin Exp Pharmacol Physiol. 2001 Jul;28(7):610-7
references.pmid: 11458889
references.citation: Mol Endocrinol. 2009 Mar;23(3):349-59
references.pmid: 19131510
references.citation: Hum Reprod. 1993 Mar;8(3):350-8
references.pmid: 8473447
references.citation: Endocrinology. 2010 Sep;151(9):4477-84
references.pmid: 20660067
references.citation: J Comp Neurol. 2009 Jan 20;512(3):347-58
references.pmid: 19003958
references.citation: Mol Endocrinol. 2006 Sep;20(9):1996-2009
references.pmid: 16645038
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17217-22
references.pmid: 19805188
references.citation: J Neurosci. 1996 May 1;16(9):3035-44
references.pmid: 8622133
references.citation: Lancet. 2005 Jul 2-8;366(9479):74-85
references.pmid: 15993236
references.citation: J Comp Neurol. 2005 Jul 4;487(3):332-44
references.pmid: 15892097
references.citation: Endocrinology. 2008 Dec;149(12):6113-24
references.pmid: 18755790
references.citation: J Neurosci. 2007 Aug 29;27(35):9294-300
references.pmid: 17728443
references.citation: Biochim Biophys Acta. 2007 Jun;1771(6):677-91
references.pmid: 17490911
references.citation: Ann N Y Acad Sci. 2005 Jun;1052:136-44
references.pmid: 16024756
references.citation: Endocrinology. 1997 Sep;138(9):4030-3
references.pmid: 9275096
references.citation: Mol Cell Endocrinol. 2009 Sep 24;308(1-2):17-25
references.pmid: 19549588
references.citation: Endocrinology. 2007 Oct;148(10):4937-51
references.pmid: 17595223
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12354-7
references.pmid: 15302933
references.citation: Trends Pharmacol Sci. 1992 May;13(5):177-84
references.pmid: 1604710
references.citation: Neuroendocrinology. 1989 Jul;50(1):51-8
references.pmid: 2547176
references.citation: J Neurosci Res. 2003 Mar 15;71(6):802-10
references.pmid: 12605406
references.citation: J Neurosci. 2005 May 18;25(20):5066-78
references.pmid: 15901789
references.citation: Endocrinology. 2009 Jan;150(1):333-40
references.pmid: 18719019
references.citation: Endocrinology. 2001 Feb;142(2):599-607
references.pmid: 11159830
references.citation: Endocrinology. 2009 Jun;150(6):2805-12
references.pmid: 19179437
references.citation: Mol Neurobiol. 2008 Aug;38(1):66-77
references.pmid: 18670908
references.citation: J Neurosci. 1992 Jul;12(7):2745-50
references.pmid: 1319480
references.citation: Endocrine. 2006 Apr;29(2):199-207
references.pmid: 16785596
references.citation: J Pharmacol Exp Ther. 2001 Oct;299(1):21-30
references.pmid: 11561059
references.citation: Endocrinology. 2009 May;150(5):2388-94
references.pmid: 19164470
references.citation: J Neurosci. 2003 Oct 22;23(29):9529-40
references.pmid: 14573532