Acute effects of phorbol esters on receptor-mediated IP3, cAMP, and progesterone levels in rat granulosa cells.
Luteinizing hormone (LH) stimulates the formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol trisphosphate (IP3) in rat granulosa cells. This report describes the effects of protein kinase C activators on second messenger generation in isolated rat granulosa cells. The protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) completely inhibited LH-stimulated inositol phosphate accumulation. The inhibitory effects of TPA were rapid (5-15 min) and concentration dependent with 50 nM TPA producing maximally inhibitory effects. However 30-min incubations with 10-100 nM TPA had no effect on LH-stimulated cAMP or progesterone levels. The inhibitory effect of TPA could not be overcome by high concentrations of LH. TPA also inhibited gonadotropin-releasing hormone-stimulated phospholipase C activity, although to a much lesser extent. Increased inositol phosphate degradation and reduced inositol phospholipid synthesis were unlikely explanations for the effects of TPA. The results indicate that phorbol esters modulate the inositol phospholipid-phospholipase C transmembrane signaling system in rat granulosa cells. The results suggest that phorbol esters may alter the coupling of the hormone receptor complex to phospholipase C.
Davis
J S
JS
Department of Internal Medicine, University of South Florida College of Medicine, Tampa.
Weakland
L L
LL
Coffey
R G
RG
West
L A
LA
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013403:Sugar Phosphates / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D006064:Gonadotropins, Equine; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D011374:Progesterone; D015544:Inositol 1,4,5-Trisphosphate; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate