Prostaglandin F2 alpha activates protein kinase C in human ovarian cells.
Recent studies in several non-primate species have suggested that prostaglandin F2 alpha (PGF2 alpha) inhibits luteal cell progesterone production by activating the calcium and phospholipid-dependent protein kinase, protein kinase C (PKC). This study investigated the presence of PKC in human ovarian cells and assessed the ability of PGF2 alpha and its structural analogue, cloprostenol, to generate inositol polyphosphates and activate PKC. PKC was detected in cultured human granulosa-lutein cells and human luteal cells (from mid-late luteal phase). The major proportion of PKC detected was cytosol-associated in both cell types. Cloprostenol increased the generation of inositol polyphosphates in cultured human granulosa-lutein cells in a dose- and time-dependent manner. In addition both cloprostenol and PGF2 alpha activated PKC (as assessed by redistribution of enzyme activity from a principally cytosol-associated form to a membrane-associated form) in both granulosa-lutein and luteal cells. Short-term exposure of both cell types to phorbol myristate acetate (4 beta-PMA) activated PKC, whilst prolonged exposure of human granulosa-lutein cells to 4 beta-PMA led to a > 85% loss of total PKC activity. The inactive phorbol ester, 4 alpha-PMA, had no effect on PKC activity when exposed to cells for up to 20 h. These results demonstrate the presence of PKC in human ovarian cells and the ability of PGF2 alpha to induce translocation/activation of this kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Abayasekara
D R
DR
Institute of Zoology, Zoological Society of London, UK.
Jones
P M
PM
Persaud
S J
SJ
Michael
A E
AE
Flint
A P
AP
D002478:Cells, Cultured; D003008:Cloprostenol / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006107:Granulosa Cells / Q000201:enzymology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008184:Luteal Cells / Q000201:enzymology; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007295:Inositol Phosphates; D003008:Cloprostenol; D015237:Dinoprost; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate