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Adrenal Steroid Biosynthesis from 4–¹⁴C—Cholesterol (in Vitro) During Phenobarbital Block of PMS-Induced Ovulation in Immature Rats¹

Department of Physiological Chemistry, Endocrinology-Reproductive Physiology Program and the Waisman Center on Mental Development, University of Wisconsin Madison, Wisconsin 53706

Abstract

Phenobarbital (PB) block of ovulation in PMS—primed (day 30) immature rats is associated with a depressed adrenal steroidogenesis in vitro. Adrenals from PB—treated (1:30 PM on day 32) and untreated rats were incubated with 4–¹⁴C—cholesterol. The incubations with PB—treated adrenals showed an appreciable decrease in the amount of radioactivity associated with progesterone, pregnenolone, 17–hydroxypregnenolone, corticosterone, deoxycorticosterone and dehydroepiandrosterone on the basis of purification to a constant specific activity with chromatographic techniques. Little, if any, ¹⁴C was associated with 17–hydroxyprogesterone, testosterone and androstenedione.

The lack of radioactivity associated with 17– hydroxyprogesterone confirms previous observations that this steroid is apparently not synthesized by rat adrenals. However, the finding of appreciable ¹⁴C associated with 17–hydroxypregnenolone in both groups of rat adrenals indicates the presence in these PMS—treated rats of adrenal 17ahydroxylase activity presumably for pregnenolone as substrate.

The decrease in adrenal progesterone production may contribute in part to the decrease in circulating progesterone that is observed in these PBtreated rats, since in the rat a large portion of circulating progesterone is attributable to adrenal production.

On the basis of these adrenal data and our previous reports on the effects of PB on the biosynthesis and metabolism of steroids by ovarian and liver tissues, it appears that PB affects all three of these major steroid producing and/or metabolizing organs. In the rat all three play a significant role in regulating progesterone levels. The action of PB in inhibiting ovulation may be due in part to its effects on steroid metabolism at all three sites so that the optimal steroid environment essential for ovulation is not attained. In addition, PB may be altering thresholds within the hypothalamus or adenohypophysis to intrinsic neural stimuli either directly or indirectly (via an altered steroidal environment). (Endocrinology 92: 1200, 1973)

Footnotes

¹ This investigation was supported by PHS Grants No. 5–TO1–HD–OO1O4–O7, 1R01–HD–05414–01A1 and 2 PO1–HD–O3352–O5 from NICHD and a Ford Foundation Grant No. 63O–5O5A.

² Dept. of Gynecology & Obstetrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461.

³ Career Development Awardee, NICHD No. 1– K4–HD–7O,OO6–O1 and to whom reprint requests should be addressed.

Received August 8, 1972.