title: Estradiol selectively regulates alpha 1B-noradrenergic receptors in the hypothalamus and preoptic area.
abstract: We previously demonstrated that estradiol administered in vivo elevates the number of alpha 1-adrenoceptors in preoptic area (POA) and hypothalamic membranes from ovariectomized female rats and potentiates alpha 1 receptor augmentation of beta-adrenoceptor-stimulated cAMP formation in slices from these brain regions. Present studies examined (1) if estradiol selectively regulates any alpha 1-adrenoceptor subtype, and (2) which alpha 1 receptor subtype mediates the augmentation of cAMP synthesis. Hypothalamic and POA membranes from estradiol-treated rats, when compared to ovariectomized rats, had modestly (30-50%) but significantly elevated numbers of 3H-prazosin (alpha 1) binding sites. Estradiol affected neither the number of alpha 1 receptor sites in frontal cortex nor the affinity of 3H-prazosin binding in any brain region examined. Results of binding studies conducted in the presence of chlorethylclonidine, a selective, irreversible inactivator of the alpha 1B receptor subtype, indicated that the estrogen-dependent increase in total alpha 1 binding sites in POA and hypothalamic membranes was attributable to a selective, five- to sixfold increase in alpha 1B receptor number. Progesterone had no measurable effects on alpha 1 receptor binding. Blockade of alpha 1B receptors with chlorethylclonidine eliminated phenylephrine augmentation of isoproterenol-stimulated cAMP formation in slices, whereas the alpha 1A antagonist 5-methyl-urapadil did not. This suggests that the alpha 1B receptor subtype potentiates cAMP formation. Thus, the increased alpha 1 receptor augmentation of cAMP formation seen in slices from estradiol-treated rats is correlated with increased alpha 1B receptor number.
authors.affiliation: Department of Psychiatry, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: N
authors.initials: N
authors.lastname: Petitti
authors.forename: G B
authors.initials: GB
authors.lastname: Karkanias
authors.forename: A M
authors.initials: AM
authors.lastname: Etgen
mesh_terms: D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D010052:Ovariectomy; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*
chemical_list: D004146:Dioxanes; D010879:Piperazines; D011941:Receptors, Adrenergic; C057446:5-methylurapidil; C051731:chlorethylclonidine; D004958:Estradiol; D000242:Cyclic AMP; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D011224:Prazosin