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.