Gonadal steroid modulation of neurotransmitter-stimulated cAMP accumulation in the hippocampus of the rat.

We have investigated the influences of gonadal and adrenal hormones on neurotransmitter-stimulated cyclic adenosine 3',5'-phosphate (cAMP) formation in hippocampal slices from male and female rats. We found that castration of male rats specifically decreases histamine-stimulated cAMP accumulation, as does administration of estradiol plus progesterone to ovariectomized female rats. In ovariectomized females, activation of cAMP accumulation by isoproterenol was also reduced by estradiol plus progesterone treatment. Although neither of these endocrine manipulations significantly affected stimulation of cAMP accumulation by vasoactive intestinal peptide (VIP), regulation of VIP-stimulated cAMP generation by glucocorticoids was found in female rats. However, the direction of the effect of the synthetic glucocorticoid dexamethasone in females was opposite to its previously demonstrated action in males. These results suggest that gonadal and other steroids may specifically modulate the responsiveness of components of the adenylate cyclase system to certain neurotransmitters, and that such regulation may differ between the sexes and may occur in telencephalic brain regions such as the hippocampus.