Human Pancreatic Tumor Growth Hormone-Releasing Factor Stimulates Anterior Pituitary Adenylate Cyclase Activity, Adenosine 3′,5′-Monophosphate Accumulation, and Growth Hormone Release in a Calmodulin-Dependent Manner*

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Abstract
Pituitary GH [growth hormone] secretion is regulated by Ca2+ and cAMP. Human pancreatic tumor GRF (hpGRF) stimulated anterior pituitary adenylate cyclase activity, cAMP accumulation, and GH release. The relationship between Ca2+ and the stimulating effects of the Ca2+ ionophore A23187 [calcimycin] on cAMP accumulation and GH release in vitro was studied. To evaluate the role of the Ca2+-binding protein calmodulin in this system, calmodulin antagonist W7, a [1-N-(6-aminohexyl)-5-chloro-1] naphthalene-sulfonamide and its less active analog W5 [N-(aminohexyl)-1-naphthalene sulfonamide] were used. W7 inhibited hpGRF-stimulated adenylate cyclase activity, cAMP accumulation, and GH release, whereas W5 was either poorly effective or ineffective. Somatostatin (SRIF) also attenuated hpGRF stimulation of adenylate cyclase. The actions of Ca2+-calmodulin and cAMP are interrelated in modulating GH release. Calmodulin participates in hpGRF stimulation of adenylate cyclase, cAMP formation, and GH release. The attenuation of hpGRF-stimulated adenylate cyclase activity by SRIF may be 1 of the mechanisms for its GH inhibitory action.