a,-Adrenoceptor Augmentation of ,&Stimulated CAMP Formation Is Enhanced by Estrogen and Reduced by Progesterone in Rat Hypothalamic Slices

These experiments examined the influence of estradiol and progesterone given in vivoon norepinephrine (NE) regulation of CAMP synthesis in hypothalamic and preoptic area slices in vitro. Administration of progesterone to estrogen-primed female rats attenuated NE-induced slice CAMP accumulation. This hormone-dependent reduction in NE-stimulated CAMP synthesis was observed in slices incubated with TTX and in slices prepared from hypophysectomized rats, suggesting that progesterone effects on NE receptor activation of CAMP-generating systems are not secondary to the release of neurotransmitters that inhibit adenylyl cyclase or to changes in pituitary hormone secretion. Progesterone suppression of NE-induced CAMP formation could be prevented by incubating slices in the presence of a phorbol ester. In additional studies, the activity of B-NE receptors was assessed by measuring isoproterenol (ISO)-stimulated CAMP accumulation in the presence of the phosphodiesterase inhibitor RO-20-1724, and the activity of a, receptors was evaluated by measuring phenylephrine (PHE) augmentation of the IS0 response. Estradiol reduced the CAMP response to IS0 in both hypothalamic and preoptic area slices, and this effect was not reversed by subsequent progesterone treatment. Estradiol also enhanced PHE augmentation of ISO-stimulated CAMP synthesis. Moreover, administration of progesterone subsequent to estradiol eliminated a,-receptor augmentation of the IS0 response. An CY, enhancement of the IS0 response is observed if the progestin receptor antagonist RU 38488 is administered before progesterone. Progesterone also abolished PHE potentiation of vasoactive intestinal polypeptide-stimulated CAMP accumulation. In contrast, neither phorbol ester nor muscarinic (carbachol) potentiation of the CAMP response to IS0 was affected by progesterone. The data suggest that ovarian steroids regulate the coupling of both (Y, and fi receptors to the membrane effector systems that generate intracellular CAMP.