Inhibition of Rat Testicular Androgen Synthesisin Vitroby Melatonin and Serotonin1

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Abstract
Carbon-14-labeled progesterone, 17α-hydroxyprogesterone, androstenedione, and testosterone were incubated with rat testicular preparations with and without serotonin or melatonin. Serotonin inhibited 17α-hydroxylase, 17α-hydroxypregnene-C17-C20-lyase, and 17-keto reductase activities. Serotonin increased 17P-hydroxysteroid dehydrogenase activity, but decreased 20α-reductase for 17α-hydroxyprogesterone. Melatonin also inhibited 17ot-hydroxylase, 17α-hydroxypregnene- C17-C20-lyase and 17β-hydroxysteroid dehydrogenase, but not 17-keto reductase activities. It increased 20a-reductase activity. Serotonin and melatonin altered the A/T ratios in the incubations. The effects of serotonin on steroid biotransformations correlated well with recent reports of the presence of serotonin in testicular tissue and with the metabolism of serotonin as it related to age changes in the rat. The differential action of serotonin and melatonin on the 17βhydroxysteroid dehydrogenase system is consistent with the hypothesis that this system is comprised of two components: one, a 17-keto reductase and the other, a 17β-hydroxysteroid dehydrogenase. Serotonin inhibited androgen synthesis through a noncompetitive inhibition while melatonin inhibited androgen synthesis through a mixed method that was mainly noncompetitive with respect to NADPH availability. Endocrinology90: 17, 1972)

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