Lowered Ovarian Conversion of14C-Pregnenolone to Progesterone and other Metabolites during Phenobarbital (PB) Block of PMS-Induced Ovulation in Immature Rats: Inhibition of 3β-Hydroxysteroid Dehydrogenation*
The effect of phenobarbital (PB) on the ovarian conversion of 4-14C-pregnenolone to progesterone, pregn-5-ene-3,20-dione, 3β-hydroxypregn- 4-en-20-one, 17-hydroxyprogesterone and 17-hydroxypregnenolone was studied in proestrous PMS-primed immature rats. The data obtained from the PB-treated groups as compared to the untreated groups showed an appreciable decrease in the amount of radioactivity associated with progesterone, pregn-5-ene-3,20-dione and 17-hydroxyprogesterone and an increased accumulation of radiolabeled pregnenolone and 17-hydroxypregnenolone. No radioactivity was associated with 3β-hydroxypregn-4-en-20-one indicating that this compound is not the intermediate in the conversion of pregnenolone to progesterone. The intermediate appears to be pregn-5-ene-3,20-dione. The results described in this paper suggest that phenobarbital is inhibiting the dehydrogenation step in the conversion of pregnenolone to progesterone. These results and others from these laboratories suggest that the action of PB in blocking ovulation may not be entirely at the neural level. The ovulation- inhibiting action of PB may be due, at least in part to the interference of normal steroidogenesis, particularly the conversion of pregnenolone, so that the optimal steroid environment essential for regulation of ovulation is not attained (Endocrinology92: 117, 1973)