Stimulation of Steroid C-11β Hydroxylase Activity in Adrenal Homogenates by Cyclic 3′,5′-Adenosine Monophosphate

Abstract

STEROID biosynthesis in the mammalian adrenal cortex is dependent on the activity of a number of complex enzyme systems, including several hydroxylases which require NADPH as cofactor¹. NADPH is continuously generated from NADP within the adrenal cortex by the action of several dehydrogenases acting on appropriate substrates². Of the latter, glucose-6-phosphate appears to be the most important³. Haynes, Koritz and Péron⁴ demonstrated that adenosine-3′,5′-monophosphate (cyclic 3′,5′-AMP) enhanced the production of corticosterone from endogenous precursors by surviving rat adrenal sections. Since cyclic 3′,5′-AMP also stimulated phosphorylase activity in adrenal slices, the effect of the nucleotide on corticosteroidogenesis was apparently related to increased provision of glucose-6-phosphate⁵. Of added significance was the observation by Haynes^5,6 that ACTH resulted in the accumulation in adrenal slices of cyclic 3′,5′-AMP, which presumably was responsible for the resulting stimulation of corticosteroidogenesis. Attempts to demonstrate a stimulatory effect of cyclic 3′,5′-AMP on corticosteroidogenesis from endogenous substrates in adrenal homogenates have hitherto been unsuccessful^4,7. In the investigations recorded here, addition of this nucleotide to rat adrenal homogenates markedly stimulated C-11β hydroxylation of added progesterone and 11-deoxycorticosterone, but appeared to have no effect on C-21 hydroxylation of progesterone.