Modulation of LH release by estradiol. Involvement of protein kinase C in the action mechanism of GnRH

The involvement of PKC in GnRH action is still controversial. Discrepancies between different results could be due to the endocrine status of cells used for the studies. In order to determine a putative role for PKC in GnRH action and if gonadal steroids could be implicated in the PKC contribution to GnRH action, we have conducted a study of LH release in response to GnRH and to PMA, an activator of PKC, using an anterior pituitary cell culture system. The direct effects of E2 were considered coupled or not with the effect of PKC depletion. GnRH and PMA induced LH releases in a dose-dependent manner. Both are increased by E2. The PKC depletion had no effect on GnRH stimulated LH release in cells deprived of gonadal steroid influence but induced a significant decrease in cells which had been treated by E2. These results indicate that E2 alters cell sensitivity to GnRH by affecting post-receptor intracellular pathways such as PKC activation.