Effects of beta-naphthoflavone and 3-methylcholanthrene administered to pregnant rats on steroid metabolism in the isolated basal zone of the placenta.

Steroid synthesis and metabolism were studied in the isolated basal zone of the rat placenta in which the steroidogenic giant trophoblast cells are localized. Incubation of [14C]progesterone with the 10,000 X g supernatant fraction of the basal zone from untreated animals resulted in formation of the following metabolites: 5 alpha-pregnane-3 alpha-ol-20-one, androstenedione, 17 alpha-hydroxy progesterone, 5 alpha-pregnane-3 beta-ol-20-one, testosterone and 5 alpha-pregnane-3,20-one. The multiple oxidized and reduced products of progesterone were resolved and radiochemically characterized by thin-layer chromatography in combination with high-pressure liquid chromatography. The administration of beta-naphthoflavone (beta-NF) and 3-methylcholanthrene (3-MC) during midgestation produced no adverse effects on maternal weight gain, fetal resorption rate, fetal body weight or basal zone weight when studied on day 15 of gestation. Both beta-NF and 3-MC treatments were associated with a 40 to 50% decrease in the formation of androstenedione, 17 alpha-hydroxy progesterone and testosterone. In addition the formation of 5 alpha-pregnane-3 alpha-ol-20-one, 5 alpha-pregnane-3 beta-ol-20-one and 5 alpha-pregnane-3,20-one was decreased by 30 to 60% in basal zone preparations from beta-NF- and 3-MC treated animals. Thus, the suppressed enzyme activities involve cytochrome P-450 dependent monooxygenase as well as 5 alpha-reductase pathways. Although neither beta-NF- nor 3-MC-treated animals showed evidence of in utero toxicity on day 15 of gestation, study of animals later in pregnancy on day 20 showed significant inhibition of late fetoplacental growth.(ABSTRACT TRUNCATED AT 250 WORDS)