Diethylstilbestrol-elicited accumulation of cyclic AMP in incubated rat hypothalamus.

Diethylstilbestrol (DES) and 17beta-estradiol elicit significant increases in levels of endogenous and [14C]cyclic AMP in [14C]adeninelabeled hypothalami from immature female rats, but only after incubation of the hypothalami with these estrogenic agents for 40-50 min. Estriol has no effect. The 2-fold accumulation of cyclic AMP elicited by low concentrations (20 muM) of DES appears dependent on catecholamine-related mechanisms, since it is prevented by either alpha- or beta-adrenergic antagonists. Higher concentrations (100 muM) of DES elicit a 3-fold accumulation of [14C]cyclic AMP which is only partially blocked by adrenergic antagonists, haloperidol, or the adenosine antagonist, theophylline. These phenomena appear to be specific for the hypothalamus since incubation of cerebral cortical slabs with estrogens resulted in no significant increases in the levels of cyclic AMP. The slow time course in whole hypothalami and the complete lack of effects of low concentrations of estrogenic agents in chopped hypothalami suggest an indirect mechanism of action. Interaction of estrogens with receptors in cell bodies may result, after a latent period of 40-50 min, in enhanced release of catecholamines from distal synaptic terminals and in stimulation of catecholamine-sensitive adenylate cyclases at post-synaptic sites.