Inhibition by staurosporine of TRH-induced refractoriness of inositol phospholipid hydrolysis in rat anterior pituitaries.

ABSTRACT

To clarify the mechanism(s) underlying the TRH-induced refractory state of the anterior pituitary, we evaluated rat pituitary inositol phospholipid hydrolysis in the presence of staurosporine. TRH caused a time- and dose-dependent accumulation of inositol phosphates in rat anterior pituitary slices. Pretreatment with 550 nmol TRH/l completely abolished the subsequent accumulation of inositol phosphates in response to 140 nmol TRH/l. TRH-stimulated accumulation of inositol phosphates did not occur after pretreatment with 0.2 mumol phorbol ester/l. Refractoriness of inositol phospholipid hydrolysis which was produced by pretreatment with TRH and phorbol ester was inhibited by staurosporine. The present data support the hypothesis that protein kinase C plays a profound role in TRH induction of the refractory state of inositol phospholipid hydrolysis in the anterior pituitary.