Studies of the effect of the cardiac glycoside, ouabain, on the release of ACTH and GH from anterior pituitary halves were performed in vitro at 37 C. Ouabain in concentrations of from 1 × 10-5 to 1 × 10-3M stimulated ACTH release in guinea pig tissue and GH release in rat tissue. Ouabain in concentrations of 5 × 10-4M and 1 × 10-3M stimulated ACTH release in rat pituitary tissue. Ouabain–induced hormone release did not occur when pituitary tissue was incubated at 4 C. Incubation of pituitary tissue in the absence of potassium increased by 10-fold the sensitivity to ouabain in terms of ACTH release and directly stimulated the release of GH. In the absence of calcium, ouabain did not stimulate ACTH and GH release. These results can be explained by an interaction of ouabain with Na+, K+–ATPase, the consequence of which is pituitary hormone release. Since ouabain promotes calcium influx in several tissues including the pituitary, and hormone release is calcium dependent, we propose that a Na+/K+ pump–mediated calcium influx modulates ACTH and GH release from the pituitary.
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