Activation of protein kinase C inhibits synthesis and release of decidual prolactin.
Activation of calcium-activated, phospholipid-dependent protein kinase C by diacylglycerol and phorbol esters has been shown to mediate release of hormones in many systems. To determine whether protein kinase C activation is also involved in the regulation of prolactin release from human decidua, we have examined the effects of various acylglycerols and phorbol esters on the synthesis and release of prolactin from cultured human decidual cells. sn-1,2-Dioctanoylglycerol (diC8), which is known to stimulate protein kinase C in other systems, inhibited prolactin release in a dose-dependent manner with maximal inhibition of 53.1% (P less than 0.01) at 100 microM. Diolein (100 microM), which also stimulates protein kinase C activity in some systems, inhibited prolactin release by 21.3% (P less than 0.05). Distearin and dipalmitin, which are much less effective in activating protein kinase C, and monopalmitin and tripalmitin, which do not activate protein kinase C, had no significant effect on prolactin release. Phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-didecanoate, and 4 beta-phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, while the protein kinase C inactivate 4 alpha-phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. The amounts of prolactin synthesized by cells exposed to diC8 (300 microM) or PMA (10(-7) M) for 30 min were 56.3 and 50.0% less than that synthesized by control cells (P less than 0.01 in each instance).(ABSTRACT TRUNCATED AT 250 WORDS)
D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D011247:Pregnancy; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology
D004075:Diglycerides; D010703:Phorbol Esters; D011388:Prolactin; D011493:Protein Kinase C