Estradiol Selectively Regulates a,,-Noradrenergic Receptors in Hypothalamus and Preoptic Area

We previously demonstrated that estradiol administered in viva elevates the number of a,-adrenoceptors in preoptic area (POA) and hypothalamic membranes from ovariectomized female rats and potentiates a, receptor augmentation of ,&adrenoceptor-stimulated CAMP formation in slices from these brain regions. Present studies examined (1) if estradiol selectively regulates any cY,-adrenoceptor subtype, and (2) which ,x, receptor subtype mediates the augmentation of CAMP synthesis. Hypothalamic and POA membranes from estradiol-treated rats, when compared to ovariectomized rats, had modestly (3040%) but significantly elevated numbers of 3H-prazosin ((Y,) binding sites. Estradiol affected neither the number of a, 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 (Y,~ receptor subtype, indicated that the estrogen-dependent increase in total a, binding sites in POA and hypothalamic membranes was attributable to a selective, fiveto sixfold increase in (Y,~ receptor number. Progesterone had no measurable effects on a, receptor binding. Blockade of alB receptors with chlorethylclonidine eliminated phenylephrine augmentation of isoproterenol-stimulated CAMP formation in slices, whereas the a,A antagonist 5methyl-urapadil did not. This suggests that the a,B receptor subtype potentiates CAMP formation. Thus, the increased (Y, receptor augmentation of CAMP formation seen in slices from estradiol-treated rats is correlated with increased (Y,~ receptor number.