MODULATION OF ACTIVIN-A ACTION AND SPECIFICITY IN THE RAT GONADOTROPEBY PROTEIN-KINASE-C

This study was undertaken to assess the role of protein kinase C (PKC) in activin action in the rat pituitary. Pretreatment with 500 nm phor bol 12-myristate 13-acetate (PMA) for 22-24 h reduced subsequent FSH a nd LH release (percentage of total cellular FSH and LH released) in re sponse to 100 nm PMA. This action persisted for 2 days after the pretr eatment. Pretreatment with 500 nM 4alpha-phorbol 12,13-didecanoate (4a lphaPDD, a phorbol ester which does not activate PKC) did not affect c ell responsiveness to 100 nm PMA. Both PKC-down-regulated cells and ce lls with a full complement of PKC responded similarly to 100 nm GnRH a nd 100 mum A23187 during this period. Incubation with 50 ng/ml activin A for 48 h significantly increased both FSH release and total FSH (ex tracellular plus intracellular) compared to corresponding basal values in PMA-pretreated cells, as well as in vehicle- or 4alphaPDD-pretreat ed cells. Activin stimulation of basal FSH release and total FSH was s ignificantly more potent in PMA-pretreated cells than in cells not pre treated with PMA. Activin did not alter basal LH release or total LH i n vehicle- or 4alphaPDD-pretreated cells but significantly increased b oth in PMA-pretreated cells. When PMA was present only during the init ial 2 h of the 22- to 24-h pretreatment period at 50 nm, PKC was not d own-regulated. In these cells, the potency of activin stimulation of b asal FSH release was not affected, but stimulation of basal LH release by activin was still observed. These results suggest that PKC is not required for activin to stimulate FSH release but is involved as a mod ulator of potency and specificity of the activin action.