PROGESTERONE MODULATION OF GONADOTROPIN-SECRETION BY DISPERSED RAT PITUITARY-CELLS IN CULTURE .3. A23187, CAMP, PHORBOL ESTER AND DIC8-STIMULATED LUTEINIZING-HORMONE RELEASE

Dispersed estradiol-treated rat pituitary cells were used to characterize progesterone (P) modulation of luteinizing hormone (LH) secretion in response to a variety of pharmacologie secretagogues which influence cell biochemistry. Acute (< 3 h) and chronic (24 h) exposures to P prior to secretagogue challenge respectively enhanced and inhibited Ca2+ iontophore (A23187)-stimulated and gonadotropin-releasing hormone (GnRH)-stimulated LH release in similar quantitative fashion without any effect on concurrent prolactin release. Similar responses were also noted with cholera toxin-stimulated secretion. However, when protein kinase C activators such as phorbol esters and dioctanoylglycerol were used to trigger LH release, chronic exposure to P did not inhibit, but rather enhanced, LH release. Again, P had no effect on prolactin release. 'Washout' studies indicated that chronic treatments with P would suppress LH secretion stimulated by these compounds, but only when the steroid was cleared from the cells 4 h beforehand. These studies provide further evidence that P specifically modulates gonadotroph secretory function via mechanisms which bypass GnRH receptors. Moreover, they suggest that P exerts many different actions within the gonadotroph and question the role of protein kinase C in GnRH action. © 1990.