Diethylstilbestrol potentiation of the dopamine-elicited formation of adenosine 3',5'-monophosphate in incubated male rat hypothalamus.

Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA.