ACTH Secretion Due to Hypothalamo-Pituitary Effects of Adenosine-3′5′-monophosphate and Related Substances1

Adenosine-3′,5′-monophosphate (cAMP) and related substances were tested for their ability to cause ACTH release upon stereotaxic microinjection into brain or adenohypophysis of dexamethasone-pretreated rats. Intrapituitary injections of the dibutyryl analog of cAMP (DBcAMP) resulted in increased ACTH secretion as indicated by plasma corticosterone levels. Significant increases in ACTH release were also seen in response to theophylline, but not to caffeine. cAMP itself in the pituitary was effective only if preceded by theophylline. Solutions containing high potassium concentrations were also effective only in theophylline- primed pituitaries. Adenosine-5′-monophosphate had no effect on ACTH secretion. Injections of theophylline and DBcAMP into the basal hypothalamus evoked responses similar to those due to the pituitary injections. All doses used had no effect on ACTH secretion when administered intravenously. Responses to both pituitary and hypothalamic injections of these substances were decreased by pretreatment with very high doses of dexamethasone. It is concluded that cAMP may play some role in the hypothalamo-pituitary mediation of ACTH secretion. (Endocrinology89: 500, 1971)