Inhibition of corticosterone formation and 3 -hydroxysteroid dehydrogenase activity in cell-free preparations of rat adrenals.

Abstract

CAMP, AMP, ADP, ATP and nicotinamide inhibited the formation of corticosterone in rat adrenal homogenates; CAMP was the most potent inhibitor. The site of inhibition was localized to the conversion of pregnenolone to progesterone. The degree of inhibition was influenced by the basal rate of corticosteroidogenesis in the absence of cyclic nucleotide and the presence of an active phosphodiesterase capable of degrading CAMP. CAMP, AMP, ATP, adenosine and nicotinamide were shown to inhibit the 3β-hydroxysteroid dehydrogenase (3β-HSD) in the rat adrenal microsomal fraction competitively with respect to the cofactor for the reaction, NAD+. CAMP was the most effective inhibitor; however, the affinity of the enzyme for the cofactor NAD+ was greater than for the cyclic nucleotide. Other kinetic parameters for the 3β-HSD activity were determined. The possibility of a significant physiologic role for 3β-HSD inhibition in the regulation of steroidogenesis is considered. (Endocrinology 89: 722, 1971)