Interactions between growth hormone-releasing factor, prostaglandin E2 and somatostatin on cyclic AMP accumulation in rat adenohypophysial cells in culture.

Synthetic human pancreatic growth hormone-releasing factor (hpGRF(1-40)-NH2) causes a 100% stimulation of cyclic AMP cell content in rat adenohypophysial cells in culture as early as 1 min after its addition while a maximal 33-fold increase is measured at 40 min. Somatostatin (10 nM) causes a 40-60% inhibition of GRF-induced cyclic AMP accumulation while GH release is inhibited by 90-95% at all time intervals. The inhibitory effect of somatostatin is exerted on the maximal effect of GRF while the ED50 values of GRF action on cyclic AMP cell content (approximately 1 nM) and GH release (approximately 0.1 nM) are not affected by the tetradecapeptide. Prostaglandin E2 causes a 2.5-fold increase in cyclic AMP levels within 1 min after its addition with a maximal 25-fold stimulation measured at 30 min. Although not completely additive, the stimulatory effects of PGE2 and GRF together on cyclic AMP cell content and GH release are more potent than when either substance is present alone. The inhibitory effects of somatostatin on PGE2 action are analogous to those observed in the presence of GRF. The present data suggest that the hypothalamic control of GH secretion by GRF and somatostatin results, at least to a large extent, from the balance between the stimulatory action of GRF and the inhibition of somatostatin on the adenylate cyclase system.