PHORBOL ESTER INHIBITION OF OVARIAN AND TESTICULAR STEROIDOGENESIS INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (3) , 885-892
Abstract
Possible influences of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) upon gonadal steroidogenesis were investigated in vitro. Granulosa cells from hypophysectomized, estrogen-treated rats were cultured for 2 days in medium containing 0.1 .mu.M androstenedione. FSH treatment increased estrogen, progesterone and 20.alpha.-hydroxypregn-4-en-3-one production. Concomitant TPA treatment inhibited FSH-stimulated estrogen production, FSH-stimulated progesterone and 20.alpha.-hydroxypregn-4-en-3-one production. N6O2''-dibutyryl cAMP increased steroidogenesis. Cotreatment with TPA blocked progestin but not estrogen production. The TPA inhibition of progestin biosynthesis was accompanied by decreases in FSH-stimulated pregnenolone biosynthesis and 3.beta.-hydroxysteroid dehydrogenase activity without decreasing the activity of 20.alpha.-hydroxysteroid dehydrogenase. In primary cultures of rat testicular cells, human chorionic gonadotropin treatment increased testosterone production 44-fold, whereas concomitant treatment with TPA inhibited testosterone production by up to 86%. Cholera toxin and N6O2''-dibutyryl cAMP also increased testosterone production, while the actions of these agents were decreased by TPA. The TPA suppression of testosterone production was associated with a decrease in accumulation of 17.alpha.-hydroxyprogesterone and androstenedione and an increase in progesterone production, suggesting a specific inhibition of 17.alpha.-hydroxylase and 17,20-lyase activities. These results demonstrate the inhibitory effects of a tumor promoter upon gonadotropin-stimulated steroidogenesis by cultured rat ganulosa and Leydig cells through specific regulation of steroidogenic enzymes. Additional studies may assist in further elucidation of cellular mechanisms associated with carcinogenesis and steroidogenesis.