Studies on Action of Somatostatin on Growth Hormone Release in Relation to Calcium and cAMP

Abstract

Summary

The effect of SRIF on GH release was studied in monolayer-cultured cells of rat anterior pituitary with respect to Ca²⁺ and cAMP metabolism. Both the basal GH release and the DBcAMP- or PGE₁-stimulated GH release showed the requirement for Ca²⁺ in the medium but were not affected by increasing Ca²⁺ over 1.8 mM. On the other hand, GH release induced by high K⁺ or A23187 also required the presence of Ca²⁺ but showed a different dependency on Ca²⁺ concentration, being increased by high Ca²⁺. SRIF inhibited almost completely both the basal and DBcAMP- or PGE¹-stimulated GH release. Although SRIF showed a partial inhibitory effect on the increment of GH release induced by high K⁺ during a short-term incubation at both 1.8 mM and high Ca²⁺, little inhibitory effect of SRIF on that was observed in 3-hr-incubation experiments. Similar results were obtained when A23187 was used in the presence of 5.4 mM Ca²⁺. In the presence of 1.8 m^M Ca²⁺, however, the increment of GH release induced by A23187 was inhibited partly during the incubation of both 30 min and 3 hr. When high K⁺ or A23187 was added together with DBcAMP or PGE₁, an additional increase in GH release occurred. Inhibition by SRIF of GH release enhanced by DBcAMP or PGE₁ was almost completely reversed by the simultaneous presence of high K⁺. Similar tendency, but less potently, was observed when A23187 was used instead of high K⁺. In regard to dependency on extracellular Ca²⁺ concentration and sensitivity to SRIF, high K⁺ and A23187 appear to enhance GH release by a mechanism different from that of DBcAMP and PGE₁. Moreover, our results confirm the previous findings that SRIF seemed to inhibit the hormone release by acting distal to the cAMP-dependent process(es) of the releasing pathway.