In:
Endocrinology, The Endocrine Society, Vol. 149, No. 11 ( 2008-11-01), p. 5335-5344
Abstract:
There is increasing recognition that estrogen exerts multifaceted regulatory effects on GnRH neurons. The acute effects of estrogen on calcium dynamics in these cells were examined using a transgenic mouse line that allows real-time measurement of intracellular calcium concentration ([Ca2+]i) in GnRH neurons in the acute brain slice preparation. 17-β-Estradiol (E2) at 100 pm–100 nm was found to activate [Ca2+] i transients in approximately 40% of GnRH neurons with an approximate 15-min latency. This effect was not replicated by E2-BSA, which limits E2 action to the membrane, 17-α-estradiol, the inactive isomer at classical estrogen receptors (ERs), or G-1 the GPR30 agonist. E2 continued to activate [Ca2+]i transients when transcription was blocked. An ER α-selective agonist was equally potent in activating [Ca2+] i transients, and E2 remained effective in ERβ knockout × GnRH-Pericam mice. E2’s activation of [Ca2+]i transients continued in the presence of tetrodotoxin, which blocks action potential-dependent transmission, but was abolished completely by the further addition of a γ-aminobutyric acid (GABA)A receptor antagonist. Exogenous GABA was found to initiate [Ca2+] i transients in GnRH neurons. Whole cell, voltage-clamp recordings of GnRH-green fluorescence protein neurons revealed that E2 generated discrete bursts of miniature inhibitory postsynaptic currents with a latency of approximately 15 min. These observations provide evidence for a new mechanism of nonclassical estrogen action within the brain. Estrogen interacts with the classical ERα at the level of the GABAergic nerve terminal to regulate action potential-independent GABA release that, in turn, controls postsynaptic calcium dynamics.
Type of Medium:
Online Resource
ISSN:
0013-7227
,
1945-7170
DOI:
10.1210/en.2008-0424
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2008
detail.hit.zdb_id:
2011695-0
Permalink