PROSTAGLANDIN-F2-ALPHA-STIMULATED AND PHORBOL 12-MYRISTATE-13-ACETATE-STIMULATED PROGESTERONE PRODUCTION BY CULTURED HUMAN LUTEAL CELLS IN THE MID-LUTEAL PHASE - PROSTAGLANDIN-F2-ALPHA INCREASES CYTOSOLIC CA2+ AND INOSITOL PHOSPHATES

While prostaglandin F2-alpha (PGF2-alpha) has been thought to be a natural luteolysin in non-primates, a luteolytic effect in the human corpus luteum is less evident. We therefore investigated the action of PGF2-alpha on monolayer cultures of human luteal cells obtained from mid-luteal phase corpora lutea. PGF2-alpha increased basal and human chorionic gonadotrophin (hCG)-stimulated progesterone production by human cultured luteal cells. A potent tumour-promoting phorbol ester, phorbol 12-myristate-13-acetate (PMA), also stimulated progesterone production by cultured human luteal cells. Although human luteal cells were incubated for 24 h with PMA, hCG was still able to stimulate the production of progesterone by PMA-pretreated cells. However, PMA pretreatment blocked the ability of PGF2-alpha to stimulate progesterone production. It is possible that the luteotrophic effect of PGF2-alpha may be mediated, in part, by the activation of protein kinase C. Addition of PGF2-alpha to suspensions of human luteal cells preincubated with myo-[2-H-3]inositol promoted an increase in labelled inositol phosphates. PGF2-alpha also rapidly increased intracellular free Ca2+ in human luteal cells loaded with the fluorescent Ca2+ probe, fura-2. We conclude that PGF2-alpha and PMA stimulate progesterone production and that PGF2-alpha increases the intracellular free calcium and inositol phosphates of human cultured luteal cells in the mid-luteal phase.