Stimulation of rat luteinizing hormone-β messenger RNA levels by gonadotropin releasing hormone. Apparent role for protein kinase C

The ability of gonadotropin releasing hormone (GnRH) to elevate cellular levels of mRNA for β-subunit of luteinizing hormone (LH) has been examined in monolayer cultures from rat pituitary. Low concentrations of GnRH (100 pM) induced a 6.8-fold increase in LH-β mRNA, while higher concentrations of GnRH were less effective. The low concentrations of GnRH (100 pM) did not result in altered GnRH receptor levels (92 ± 12% compared to controls) after 24 h treatment but did increase protein kinase C activity to 249 ± 16%. The protein kinase C activatory, phorbol 12-myristate 13-acetate, at concentrations (2-20 nM) which did not deplete protein kinase C, stimulated LH-β mRNA levels 2-5 fold after 24 h. Higher concentrations of phorbol 12-myristate 13-acetate, which depleted protein kinase C activity, substantially reduced the ability of 100 pM GnRH to stimulate increases in LH-β mRNA levels. As previously observed, protein kinase C-depleted cells exhibited normal LH release in response to GnRH stimulation. These studies demonstrate that low concentrations of GnRH may have an important role in regulation of gonadotropin biosynthesis. Furthermore, the results suggest that activation of protein kinase C is sufficient to stimulate increases in LH-β mRNA levels and that protein kinase C is necessary for normal GnRH stimulation of LH-β mRNA levels. Accordingly, we postulate that protein kinase C may mediate the action of GnRH on LH-β mRNA levels.