Release of Pituitary Growth Hormone by Prostaglandins and Dibutyryl Adenosine Cyclic 3′:5′-Monophosphate in the Absence of Protein Synthesis

Abstract

Effects of prostaglandins on the incorporation of [4,5-(3)H]leucine into growth hormone and its subsequent release into the incubation medium were studied. Incubation of rat anterior pituitary glands with 10(-6) M prostaglandin PGE(1) in tissue culture medium 199 for 7 hr caused a 40-300% increase in the release of labeled growth hormone into the incubation medium. PGE(1) at 10(-8) M increased growth hormone synthesis but not release. At 10(-6) M, PGE(2) had effects similar to PGE(1); PGA(1) increased growth hormone synthesis but not release. PGF(2alpha) was without effect on either synthesis or release of growth hormone.Prolactin synthesis and release were not affected by prostaglandins. All of the prostaglandins, at 10(-4) M, increased adenyl cyclase activity in the pituitary gland but phosphodiesterase activity was unaltered. Dibutyryl cyclic AMP, with or without caffeine, caused an up to 300% increase in labeled growth hormone release. No consistent effect of prolactin was observed. If potassium concentration was increased 10-fold, a 215% increase in growth hormone release was observed. A combination of hypertonic potassium and 10(-6) M PGE(1) increased growth hormone release 325%, suggesting that potassium and prostaglandins act by independent mechanisms. Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone. Although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone. Similarly, puromycin inhibited synthesis of growth hormone but did not block release induced by prostaglandin, dibutyryl cyclic AMP, theophylline, or fluoride. Prostaglandins increase pituitary adenyl cyclase activity and, presumably via cyclic AMP, increase growth hormone release, independently of protein synthesis.