Effect of phorbol ester on the regulation of [formula omitted] receptors

Abstract

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.