Steroid Biosynthesis and Metabolism during Phenobarbital (PB) Block of PMS—Induced Ovulation in Immature Rats*

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Abstract
Phenobarbital (PB) block of ovulation in PMS—primed (day 30) immature rats is associated with altered ovarian steroidogenesis from 144–C—cholesterol and liver metabolism of 144–C—progesterone. Ovaries from PB—treated (1:30 PM on day 32) and untreated rats were incubated with 144–C—cholesterol. The incubations with the PB—treated ovaries showed a decreased accumulation of the following steroids: 1) progesterone; 2) 20a—hydroxypregn–4–en–3–one; 3) dehydroepiandrosterone; 4) androstenedione; 5) testosterone; 6) estrone; 7) 173–estradiol; and 8') estriol and an increased accumulation of pregnenolone and 17–hydroxypregnenolone, as compared to the PB untreated controls. Liver tissue from these same rats when incubated with 144–C–progesterone showed in the PB—treated group an increased metabolism of progesterone and an increased conversion of progesterone to pregnenolone ( a reversal not previously shown in liver), as compared to rats not treated with PB. The higher hepatic conversion of progesterone was not associated, however, with an increased conversion to 6β–hydroxyprogesterone, 16α–hydroxyprogesterone, 5α–apregnane– 3,20–dione, or 3α–hydroxy–5α–pregnan–20– one. These data support and extend our previous in vivo findings that when PB is given just prior to the critical period it decreases the level of circulating progesterone on day 32 while increasing blood pregnenolone. The results described in this and other reports from our laboratory suggest that the primary action of PB in blocking ovulation may not be entirely at the neural level. The ovulation—inhibiting action of PB and other neuropharmacological agents may in part be due to their interference in the conversion of pregnenolone and subsequent metabolites so that the optimal steroid environment essential for the regulation of ovulation is not attained and/or that these drugs may in addition alter thresholds within the hypothalamus to intrinsic neural stimuli via an altered steroidal environment. (Endocrinology91: 157, 1972)

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