Fetal adrenal steroidogenesis: drug effects in sheep

The influence of ACTH (100 pg/ml), ethanol (10(-3)/M) and morphine (10(-6)/M) on the rate of formation of cholesterol and various steroids in female fetal adrenal tissue was studied in vitro. ACTH and ethanol had no effect on corticosterone formation, while morphine increased it significantly (0.586 +/- 0.049 to 0.799 +/- 0.027 microM/mg protein) (P less than 0.02). Cholesterol formation was increased significantly by ethanol (from 0.103 +/- 0.079 to 0.248 +/- 0.035 microM/mg protein) (P less than 0.01) but not by morphine. Both ethanol and morphine significantly decreased testosterone synthesis (from 0.079 +/- 0.043 to 0.019 +/- 0.002 and 0.006 +/- 0.003 microM/mg protein, respectively) (P less than .01, less than .001). Adrenocortical formation of 17-beta estradiol was similarly attentuated by both ethanol (from 0.372 +/- 0.056 to 0.948 +/- 0.024 microM/mg protein) and morphine (to 0.600 +/- 0.020 microM/mg protein). Adrenocortical pregnanediol formation was significantly decreased by both ethanol (50%; P less than .01) and morphine (36%; P less than .02). Thus, the effect of ethanol and morphine on testosterone, estradiol and pregnanediol was similar and consisted of suppression. The effects of these agents upon corticosterone and cholesterol formation were different. Ethanol, like ACTH, did not stimulate corticosterone formation, but such stimulation did occur with morphine. Ethanol, but not morphine, stimulated cholesterol formation. The data suggest that agents capable of placental transport affect the formation of adrenocortical hormones in the fetal adrenal.