Direct effects of medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) on rat testicular steroidogenesis

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Abstract
The effects of MPA [medroxyprogesterone acetate] and MGA [megestrol acetate] on rat testicular steroidogenesis were examined by studying: serum testosterone on HCG [human chorionic gonadotropin] primed animals treated with MPA or MGA, testosterone synthesis in rat Leydig cells cultured with MPA or MGA, MPA and MGA binding to rat testis microsomal cytochrome P-450 and MPA and MGA inhibition of enzymes of rat testicular steroidogenesis. In immature rats receiving 1.0 IU of hCG per day 20 mg/kg of MPA and MGA reduced serum testosterone by 57 and 56%, respectively. In mature male rats receiving 50.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 40 and 29%, respectively. In rat interstitial cells cultured with 10 ng of rat LH [lutropin] 1 .mu.M MPA or MGA inhibited testosterone production by 32 and 23%, respectively. Addition of MPA or MGA to microsomal preparations resulted in a type I cytochrome P-450 difference spectrum MPA and MGA inhibited rat testicular 17.alpha.-hydroxylase, 17,20-lyase and the 3.beta.- and 17.beta.-hydroxysteroid dehydrogenases. These findings suggest that MPA and MGA inhibit rat testicular steroidogenesis in vivo and in vitro. MPA and MGA are 2 clinically important synthetic 6-methyl progestins. The 6-methyl progestins have been given to boys and men for the treatment of a variety of disease states: precocious puberty, prostatic hypertrophy and sex offending behavior.

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