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)-releasing hormone (GRH)-induced GH secretion and cyclic adenosine monophosphate (cAMP) production in three pituitary adenomas and thyrotropin-releasing hormone (TRH)- and corticotropin-releasing hormone (CRH)-induced redistribution of protein kinase C (PKC) from cytosol to membrane in a pituitary adenoma resected from patients with acromegaly. GRH stimulated GH secretion in accordance with cAMP production in three cases, whereas 12-O-tetradecanoyl phorbol-13 acetate (TPA) stimulated GH secretion with cAMP production in one case. Simultaneous addition of GRH and TPA enhanced cAMP production in three pituitary adenomas. Moreover, addition of TPA with GRH resulted in additive secretion of GH in vitro. In one case, we were able to measure PKC activity and prove translocation of PKC stimulated by TRH and CRH in accordance with GH secretion in vitro and in vivo. These results suggest that TPA, an activator of PKC, has a stimulatory effect on GRH-induced cAMP production and that, finally, TRH- and CRH-induced PKC activation may cause greater secretion of GH by enhancement of cAMP production in human GH-hypersecreting adenoma cells.