Progesterone, but not estrogen, modulates the cAMP system mediated ir-beta-endorphin secretion and POMC mRNA expression from rat hypothalamic cells in culture.

It is now evident that hypothalamic beta-endorphin (beta EP) modulates reproductive physiology at the central level by inhibiting the function of neurons producing gonadotropin-releasing hormone (GnRH). Increasing evidence suggests that gonadal steroids, which play an important role in the long-loop negative feedback on the hypothalamus-pituitary-gonadal axis, may exert its indirect inhibitory action through modulating the production and release of hypothalamic beta EP. However, it remains unclear whether progesterone or estrogen alone or their combination is important to exert this effect. Employing long-term monolayer neonatal hypothalamic cell cultures, we reported here that whereas progesterone significantly enhanced forskolin-, N6,2'-O-dibutyryladenosine-3'5'-cyclic monophosphate [(Bu)2cAMP]-, 3-isobutyl-1-methylxanthine (IBMX)- or cholera toxin-stimulated immunoreactive (ir)-beta EP release from cultures treated daily for 4 consecutive days, the steroid alone produced little effect. This potentiation of progesterone was time-related and dose-dependent with an EC50 value of the steroid being approximately 25 nM; at this concentration the steroid increased ir-beta EP secretion about 1.6 times (P < 0.05) that induced by 5 microM forskolin alone. Similar effects were also observed for POMC mRNA levels in cultures subjected to 6 h of the above treatment regime. This potentiating effect appears specific as it can be mimicked by progestin, a progesterone receptor agonist and blocked by the progesterone receptor antagonist RU38486, but not RU28318, a mineralocorticoid receptor antagonist. Furthermore, beta-estradiol alone failed to exert a significant effect on basal, forskolin-induced or on forskolin and progesterone co-stimulated beta EP release or POMC mRNA levels in hypothalamic cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)