Presence of an Adenylate Cyclase Dually Regulated by Somatostatin and Human Pancreatic Growth Hormone (GH)-Releasing Factor in GH-Secreting Cells

Abstract

We have investigated the effects of SRIF and human pancreatic GH-releasing factor-44 (hpGRF-44) on adenylate cyclase (AC) activity of male rat anterior pituitaries (in which somatbtrophs are present in large proportion) and of human GH-secreting pituitary adenomas (which are almost homogeneously constituted by somatotrophs). The adenoma’s responsiveness to both agents in terms of secretion was previously demonstrated in in vitro experiments. SRIF inhibited in a dosedependent fashion the GH release from monolayer cultures of the tumors. The inhibition ranged from 32–66% at the maximal effective concentration (10⁻⁶m). hpGRF-44 stimulated GH release in a dose-dependent fashion. The stimulation was 78–172% at 10⁻⁷m. SRIF and hpGRF-44 markedly affected AC activity in both systems. SRIF elicited a pronounced inhibition of the enzyme activity in a dose-dependent manner. The inhibition was about 40% in the rat and ranged from 16–49% in adenomas at the maximal effective concentration (10⁻⁵m SRIF). The inhibitory effect was GTP-dependent. hpGRF-44 markedly stimulated AC activity. The stimulation was dose dependent and GTP dependent. The stimulation was about 650% in the rat and 26–350% in adenomas at the maximal effective concentration (10⁻⁶m). These results suggest 1) the presence of a dually regulated (by SRIF and hpGRF-44) AC in GH-secreting cells; 2) an involvement of cAMP in the intracellular mechanisms transducing the signals of SRIF and hpGRF-44 in somatotrophs. (Endocrinology115: 1203–1209, 1984)