Role of cyclic nucleotides in the inhibition of growth-hormone secretion by somatostatin.

The effects of somatostatin on GH secretion, cyclic AMP and cyclic GMp concentrations in dispersed bovine anterior pituitary cells were studied following activation of adenylate cyclase with cholera toxin and inhibition of phosphodiesterase with isobutylmethylxanthine (IBMX). Cholera toxin (10(-5)M) increased intracellular cyclic AMP concentration 10-fold and cyclic GMP concentration 3-fold relative to control, and stimulated the secretion of GH. IBMX (10(-4) M) als increased intracellular concentrations of both cyclic AMP and cyclic GMP and the secretion of GH and potentiated the actions of cholera toxin particularly in raising intracellular cyclic AMP concentrations which were elevated 40-fold in the presence of cholera toxin and IBMX. Somatostatin (5 X 10(-7) M) completely prevented GH secretion elicited by cholera toxin and/or IBMX. Somatostatin was without effect on control cyclic AMP and cyclic GMp concentrations and on the increases in both cyclic AMP and cyclic GMP caused by cholera toxin and by IBMX alone, or in combination. The data suggest that bovine GH secretion is increased when concentrations of either or both cyclic nucleotides are elevated within the cells, although incubation of cells with extracellular concentrations of cyclic AMP and cyclic GMP derivatives up to 2 x 10(-3) M caused only small changes in GH release. We suggest that somatostatin inhibits cholera toxin-induced bovine GH secretion by preventing activation of the secretory process by either cyclic AMP or cyclic GMP.