Modulation by cortisol of luteinizing hormone secretion from cultured porcine anterior pituitary cells: effects on secretion induced by phospholipase C, phorbol ester and cAMP.

Cultures of enzymatically dispersed porcine anterior pituitary cells were used to examine the effects of cortisol on luteinizing hormone secretion induced by a variety of compounds which activate different intracellular signal transduction mechanisms. Cells were pre-incubated with or without cortisol (200 micrograms/ml) for 3 days, washed and then incubated for 4 h with or without cortisol in the presence or absence of these compounds. Luteinizing hormone in the media was assayed by radioimmunoassay. Cortisol treatment had no effect on basal luteinizing hormone release, but reduced gonadotropin-releasing hormone (8.5 x 10(-8) mol/l) stimulated luteinizing hormone secretion. Phospholipase C, 8-bromo-cyclic adenosine 3',5'-monophosphate, and 12-O-tetradecanoyl-phorbol-13-acetate (an activator of protein kinase C) all stimulated luteinizing hormone secretion in a dose-dependent manner in cortisol-untreated cells. Pretreatment with cortisol inhibited luteinizing hormone secretion induced by phospholipase C and 8-bromo-cyclic adenosine 3',5'-monophosphate, but did not affect the secretion of luteinizing hormone in response to 12-O-tetradecanoyl-phorbol-13 acetate. Cortisol inhibited GnRH-induced inositol phosphate production. Our results suggest that the inhibitory action of cortisol on stimulus-coupled luteinizing hormone secretion may be exerted at two different intracellular sites: (1) by inhibition of phospholipase C activity and (2) at a point distal to cyclic adenosine 3',5'-monophosphate generation.