Adrenal Steroidogenic Actions of Cyclic Nucleotide Derivatives in the Rat

Abstract

Fifteen 3'',5''-cyclic nucleotides and related compounds were studied for ability to mimic the steroidogenic action of ACTH in rats in which secretion of ACTH and corticosterone were suppressed by treatment with .beta.-methasone or by hypophysectomy. S.c. administration of 8-chloro-c[cyclic]AMP, at doses of 40 mg/kg or greater, elicited the secretion of corticosterone to normal plasma levels in both .beta.-methasone-treated and hypophysectomized animals. cAMP, dbcAMP [dibutyryl cAMP] 8-methylthio-cAMP, 8-hydroxy-cAMP and the 6-chloro-8-aminopurine cyclic ribotide analog of cAMP also displayed steroidogenic activity in the .beta.-methasone-treated rat; cGMP 8-bromo-cGMP and 8-benzylthio-cGMP were inactive. Each of the steroidogenic derivatives of cAMP also displayed ability to activate steroidogenesis in isolated rat adrenal cells. Various derivatives of cAMP mimic adrenal steroidogenic parisons support a steroidogenic mechanism involving direct activation by the nucleotides of cAMP-dependent protein kinase of the adrenal cortex.