Journal of Neuroscience, Vol 10, 2842-2849, Copyright © 1990 by Society for Neuroscience
Alpha 1-adrenoceptor augmentation of beta-stimulated cAMP formation is enhanced by estrogen and reduced by progesterone in rat hypothalamic slices
N Petitti and AM Etgen
Departments of Psychiatry, Albert Einstein College of Medicine, Bronx, New York 10461.
These experiments examined the influence of estradiol and progesterone
given in vivo on 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 beta-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 alpha 1 receptors was evaluated by measuring phenylephrine
(PHE) augmentation of the ISO response. Estradiol reduced the cAMP response
to ISO 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 alpha 1-receptor
augmentation of the ISO response. An alpha 1 enhancement of the ISO
response is observed if the progestin receptor antagonist RU 38486 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 ISO was affected by progesterone. The
data suggest that ovarian steroids regulate the coupling of both alpha 1
and beta receptors to the membrane effector systems that generate
intracellular cAMP.