GROWTH-HORMONE SECRETION IN HUMAN ACROMEGALIC PITUITARY-ADENOMAS - CYCLIC ADENOSINE-MONOPHOSPHATE AND PROTEIN-KINASE-C RESPONSES

We examined the effect of phorbol ester on growth hormone (GH)-releasi ng hormone (GRH)-induced GH secretion and cyclic adenosine monophospha te (cAMP) production in three pituitary adenomas and thyrotropin relea sing hormone (TRH) and corticotropin-releasing hormone (CRH) induced r edistribution of protein kinase C (PKC) from cytosol to membrane in a pituitary adenoma resected from patients with acromegaly. GRH stimulat ed GH secretion in accordance with cAMP production in three cases, whe reas 12-O-tetradecanoyl phorbol 13 acetate (TPA) stimulated GH secreti on with cAMP production in one case. Simultaneous addition of GRH and TPA enhanced cAMP production in three pituitary adenomas. Moreover, ad dition of TPA with GRH resulted in additive secretion of GH in vitro. In one case, we were able to measure PKC activity and prove translocat ion of PKC stimulated by TRH and CRH in accordance with GH secretion i n vitro and in vivo. These results suggest that TPA, an activator of P KC, has a stimulatory effect on GRH induced cAMP production and that, finally, TRH- and CRH-induced PKC activation may cause greater secreti on of GH by enhancement of cAMP production in human GH hypersecreting adenoma cells. (C) 1996 by W.B. Saunders Company