Effect of phorbol ester on the regulation of LH/hCG receptors.
Granulosa cells have been used to study the regulation of LH/hCG receptor protein and mRNA expression. Phorbol 12-myristate 13-acetate (PMA) dose-dependently attenuates the increases in LH/hCG receptor mRNA and protein induced by FSH and forskolin (FSK). The presence of PMA caused a decrease in cAMP production stimulated by FSH and FSK. These results suggest that PMA-mediated decreases in cAMP are a major factor in PMA-mediated decreases in LH/hCG receptor mRNA. On the other hand, in the presence of 8-Br-cAMP, PMA significantly increased LH/hCG receptor mRNA and protein, with maximal stimulation between PMA concentrations of 3 to 30 nM (1.5 fold) with 8-Br-cAMP. These findings suggest that activation of protein kinase C by PMA attenuates the increase in cAMP accumulation induced by FSH but enhances the effect of cAMP on LH/hCG receptor expression, and that the inhibitory and stimulatory effects of PMA on LH/hCG receptor content are correlated with regulation of LH/hCG receptor mRNA levels. Since the half-life study revealed no change in the stability of the LH/hCG receptor mRNA following PMA treatment, a change in the rate of LH/hCG receptor gene transcription must be responsible for the change in the LH/hCG receptor mRNA levels.
Nakamura
K
K
Department of Obstetrics and Gynecology, Gunma University School of Medicine, Maebashi, Japan.
Minegishi
T
T
Tano
M
M
Kishi
H
H
Kameda
T
T
Miyamoto
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D012333:RNA, Messenger; D011974:Receptors, LH; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D005640:Follicle Stimulating Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate