In:
Molecular Endocrinology, The Endocrine Society, Vol. 22, No. 10 ( 2008-10-01), p. 2250-2259
Abstract:
Estradiol (E2) acts as a potent feedback molecule between the ovary and hypothalamic GnRH neurons, and exerts both positive and negative regulatory actions on GnRH synthesis and secretion. However, the extent to which these actions are mediated by estrogen receptors (ERs) expressed in GnRH neurons has been controversial. In this study, Single-cell RT-PCR revealed the expression of both ERα and ERβ isoforms in cultured fetal and adult rat hypothalamic GnRH neurons. Both ERα and ERβ or individual ERs were expressed in 94% of cultured fetal GnRH neurons. In adult female rats at diestrus, 68% of GnRH neurons expressed ERs, followed by 54% in estrus and 19% in proestrus. Expression of individual ERs was found in 24% of adult male GnRH neurons. ERα exerted marked Gi-mediated inhibitory effects on spontaneous action potential (AP) firing, cAMP production, and pulsatile GnRH secretion, indicating its capacity for negative regulation of GnRH neuronal function. In contrast, increased E2 concentration and ERβ agonists increase the rate of AP firing, GnRH secretion, and cAMP production, consistent with ERβ-dependent positive regulation of GnRH secretion. Consonant with the coupling of ERα to pertussis toxin-sensitive Gi/o proteins, E2 also activates G protein-activated inwardly rectifying potassium channels, decreasing membrane excitability and slowing the firing of spontaneous APs in hypothalamic GnRH neurons. These findings demonstrate that the dual actions of E2 on GnRH neuronal membrane excitability, cAMP production, and GnRH secretion are mediated by the dose-dependent activation of ERα and ERβ expressed in hypothalamic GnRH neurons.
Type of Medium:
Online Resource
ISSN:
0888-8809
,
1944-9917
DOI:
10.1210/me.2008-0192
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2008
detail.hit.zdb_id:
1492112-1
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