title: Rapid actions of oestrogen on gonadotropin-releasing hormone neurons; from fantasy to physiology?
abstract: Oestradiol (E2) exerts critical homeostatic feedback effects upon gonadotropin-releasing hormone (GnRH) neurons to maintain fertility. In the female, E2 has both negative and positive feedback actions to suppress and stimulate GnRH neuron activity at different times of the ovarian cycle. This review summarizes reported rapid E2 effects on native embryonic and adult GnRH neurons and attempts to put them into a physiological perspective. Oestrogen has been shown to rapidly modulate multiple processes in embryonic and adult GnRH neurons including intracellular calcium levels, electrical activity and specific second messenger pathways, as well as GnRH secretion itself. Evaluation of in vivo data suggests that there is no essential role for rapid E2 actions in the positive feedback mechanism but that they may comprise part of the negative feedback pathway. Adult GnRH neurons are only likely to be exposed to E2 from the gonads via the circulation with appropriate physiological E2 concentrations in the rodent being 10-50 pM for negative feedback ranging up to 400 pM for positive feedback. Although most studies to date have examined the effects of supraphysiological E2 levels on GnRH neurons, there is accumulating evidence that rapid E2 actions may have a physiological role in suppressing GnRH neuron activity.
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, PO Box 913, Dunedin, New Zealand. allan.herbison@stonebow.otago.ac.nz
authors.forename: Allan E
authors.initials: AE
authors.lastname: Herbison
mesh_terms: D000818:Animals; D004967:Estrogens / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D008597:Menstrual Cycle / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone
references.citation: Endocrinology. 2008 Nov;149(11):5328-34
references.pmid: 18635656
references.citation: J Neurosci. 2009 Apr 29;29(17):5616-27
references.pmid: 19403828
references.citation: Endocrinology. 2005 Oct;146(10):4312-20
references.pmid: 15976055
references.citation: Endocrinology. 1999 Feb;140(2):652-9
references.pmid: 9927290
references.citation: Endocrinology. 1995 May;136(5):2341-4
references.pmid: 7720682
references.citation: J Neurosci. 2003 Jul 2;23(13):5771-7
references.pmid: 12843281
references.citation: Front Neuroendocrinol. 2001 Oct;22(4):292-308
references.pmid: 11587554
references.citation: Annu Rev Physiol. 2008;70:213-38
references.pmid: 17988212
references.citation: Endocrinology. 1997 Dec;138(12):5408-14
references.pmid: 9389526
references.citation: Front Neuroendocrinol. 2005 Sep;26(2):65-84
references.pmid: 16009409
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7221-6
references.pmid: 19359483
references.citation: J Neuroendocrinol. 2005 Apr;17(4):238-45
references.pmid: 15842235
references.citation: J Endocrinol. 1989 Dec;123(3):375-82
references.pmid: 2691622
references.citation: J Endocrinol. 1980 Sep;86(3):511-24
references.pmid: 7000953
references.citation: Brain Res. 2006 Dec 18;1126(1):2-26
references.pmid: 16978590
references.citation: Rev Reprod. 1998 May;3(2):130-40
references.pmid: 9685192
references.citation: Endocrinology. 2008 Nov;149(11):5335-44
references.pmid: 18703628
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8173-7
references.pmid: 17470805
references.citation: Mol Cell Endocrinol. 2006 Jul 25;254-255:32-8
references.pmid: 16781054
references.citation: Endocr Rev. 1999 Jun;20(3):279-307
references.pmid: 10368772
references.citation: Neuron. 2006 Oct 19;52(2):271-80
references.pmid: 17046690
references.citation: Trends Neurosci. 2006 May;29(5):241-9
references.pmid: 16580076
references.citation: Endocr Rev. 1998 Jun;19(3):302-30
references.pmid: 9626556
references.citation: Biol Reprod. 1997 Feb;56(2):303-9
references.pmid: 9116125
references.citation: J Neuroendocrinol. 2009 Mar;21(4):316-21
references.pmid: 19207808
references.citation: Rev Neurosci. 2008;19(6):413-24
references.pmid: 19317180
references.citation: Brain Res Bull. 1984 Apr;12(4):399-407
references.pmid: 6203621
references.citation: Brain Res. 1973 Apr 27;53(2):343-52
references.pmid: 4706033
references.citation: Brain Res. 1976 Sep 10;114(1):152-7
references.pmid: 986858
references.citation: J Comp Neurol. 1996 Jun 17;370(1):71-84
references.pmid: 8797158
references.citation: Neuroendocrinology. 1984 Feb;38(2):152-7
references.pmid: 6371570
references.citation: J Neurosci. 2004 Jul 14;24(28):6326-33
references.pmid: 15254088
references.citation: Mol Endocrinol. 2009 Mar;23(3):349-59
references.pmid: 19131510
references.citation: Endocrinology. 2008 Mar;149(3):1155-62
references.pmid: 18079199
references.citation: Endocrinology. 2005 Feb;146(2):558-63
references.pmid: 15539555
references.citation: Endocrinology. 1975 Jan;96(1):50-6
references.pmid: 1109905
references.citation: Annu Rev Physiol. 2004;66:291-313
references.pmid: 14977405