Regional specificity of gamma-aminobutyric acid receptor regulation by estradiol.
In vitro quantitative autoradiography and the microdissection technique of Palkovitz were used to examine the effects of estradiol-17 beta on GABAA receptors and on glutamic acid decarboxylase in discrete areas of rat brain. Under the conditions examined, estradiol did not affect glutamic acid decarboxylase activity. However, treatment with estradiol decreased GABAA receptor binding in a majority of areas that contain high levels of intracellular estradiol receptors and in a number of areas that contain few or no estradiol receptors. Within one brain area, the ventromedial nucleus of the hypothalamus, the estradiol effect was mapped and found to occur within the estradiol-sensitive ventrolateral portion and the surrounding dendritic plexus. Time- and dose-response relationships were region specific suggesting that estradiol might influence GABAA-receptor binding through multiple mechanisms. Estradiol does not appear to interact directly with GABAA receptors since addition of estradiol to the assay system did not affect binding. Our findings suggest that one way estradiol might affect neuroendocrine and other centrally mediated processes is through effects on GABAA-receptor binding.
O'Connor
L H
LH
Rockefeller University, New York, N.Y.
Nock
B
B
McEwen
B S
BS
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D066298:In Vitro Techniques; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D011963:Receptors, GABA-A; D009118:Muscimol; D004958:Estradiol; D005968:Glutamate Decarboxylase