Antagonism of prostaglandin-promoted pituitary cyclic amp accumulation and growth hormone secretion [formula omitted] by 7-oxa-13-prostynoic acid

Abstract

The studies reported here confirm the previously observed potent stimulus to growth hormone (GH) secretion by prostaglandin E 1 (PGE 1). Proportional increments in GH secretion were observed following in vitro addition of PGE 1 over a concentration range of 10 −7 to 10 −5 M. Growth hormone secretion could not be further stimulated by higher concentrations of prostaglandin. Prostaglandin E 1 also increased cyclic AMP concentration in the pituitary explants in a proportional fashion, which correlated closely with its potency as a growth hormone secretogogue. In order to define more precisely the mechanism by which prostaglandin acts, the effects of prostaglandin antagonist, 7-oxa-13-prostynoic acid, on GH secretion and cyclic AMP accumulation were investigated. Addition of the antagonist alone had no consistent effects on GH secretion or cyclic AMP levels in the pituitary. However, the antagonist significantly reduced the stimulation of hormone release and cyclic AMP accumulation found following addition of PGE 1. Increasing the concentration of antagonist further diminished prostaglandin stimulated hormone release and nucleotide accumulation. The antagonist failed to block the stimulatory effects of theophylline and dibutyryl cyclic AMP on GH release, indicating that the inhibition observed occurred prior to intracellular accumulation of the cyclic nucleotide. These results are consistent with the hypothesis that a prostaglandin receptor on the pituitary somatotrope is linked to the adenyl cyclase-cyclic AMP system.