AJP - Endocrinology and Metabolism, Vol 256, Issue 3 E368-E374, Copyright © 1989 by American Physiological Society
Acute effects of phorbol esters on receptor-mediated IP3, cAMP, and progesterone levels in rat granulosa cells
J. S. Davis, L. L. Weakland, R. G. Coffey and L. A. West
Department of Internal Medicine, University of South Florida College of Medicine, Tampa.
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.
