The Effect of Adenosine 3', 5'-Monophosphate and of N⁶-2'-O-Dibutyryl-Adenosine 3',5'-Monophosphate on the Mouse Ovarian Δ⁵-3β-Hydroxysteroid Dehydrogenase[*]

Abstract

Adenosine 3',5'-monophosphate (3',5'-AMP) inhibited the conversion of pregnenolone to progesterone and of dehydroepiandrosterone to Δ⁴-androstenedione in vitro system. Under similar conditions N⁶-2-O-dibutyryl-adenosine 3',5'-monophosphate (dibutyryl 3', 5'-AMP) had no effect on the enzymic reaction. The inhibition of Δ⁵-3 β-hydroxysteroid dehydrogenase by 3', 5'-AMP was released by increasing the concentrations of exogenous NAD⁺. 3', 5'-AMP and dibutyryl 3', 5'-AMP given subcutaneously 2 mg/female immature mouse twice daily for five days, had no effect on the ovarian conversion of pregnenolone to progesterone, whereas the synthesis of Δ⁴-androstenedione from dehydroepiandrosterone was inhibited by 3', 5'-AMP and to a lesser extent by dibutyryl 3', 5'-AMP. Human chorionic gonadotropin (HCG) administered in vivo stimulated the mouse ovarian Δ-3β-hydroxysteroid dehydrogenase. The physiological significance of the inhibition by the 3', 5'-AMP of the NAD⁺ dependent steroid dehydrogenase is discussed.

Adenosine 3',5'-Monophosphate - N⁶-2'-0-Dibutyryl-Adenosine 3',5'-Monophosphate-Δ⁵-3β-Hydroysteroid Dehydrogenase - Δ⁵-3-Ketosteroid-Isomerase - Pregnolone - Progesterone - Dehydroepiandrosterone - Δ⁴-Androstenedione - Human Chorionic Gonadotropin

1 This work was supported by Ford Foundation Grant No. 67-470.