Release of Growth Hormone from Purified Somatotrophs: Use of High K+and the Ionophore A23187 to Elucidate Interrelations among Ca++, Adenosine 3′,5′-Monophosphate, and Somatostatin*

Abstract

Studies were carried out to further define the sites of interaction of Ca⁺⁺, cAMP, and somatostatin (SRIF) in the mechanisms governing GH release from acutely dispersed purified somatotrophs obtained from rat adenohypophyses. Both high [K⁺] and the Ca⁺⁺ ionophore A23187 stimulated the release of GH. The release induced by high [K⁺] was accompanied by a small but significant transient increase in intracellular cAMP, while A23187 did not alter basal cAMP levels. The augmented release of GH induced by both secretagogues was blocked by SRIF (1 ng/ml) and by removing Ca⁺⁺ from the incubation medium (+] was not blocked by SRIF or by low Ca⁺⁺ incubation. These results are consistent with a model whereby an increase in free cytosol Ca⁺⁺ will result in GH release by exocytosis. This increase in free cytosol Ca⁺⁺ can come from either intracellular bound Ca⁺⁺ or from the extracellular compartment. Secretagogues which act via cAMP increase intracellular cAMP levels. The increase in cAMP would then stimulate the translocation of Ca⁺⁺ from a bound to a free cytosol form. Secretagogues may also stimulate GH release by bypassing cAMP to increase free cytosol Ca⁺⁺ by directly increasing the influx of Ca⁺⁺ into the cells or by increasing the intracellular movement of Ca⁺⁺ to the free cytosol compartment. SRIF would block GH release byacting at the level of the plasma membrane to block Ca⁺⁺ influx and by inhibiting a step(s) subsequent to the increase in cytosol Ca⁺⁺.