Changes in C21-Steroid Metabolism by Ovine Placentas During Cortisol Administration1

Abstract

Placental cotyledons were removed from 23 ewes of 120-130 days of gestation at intervals up to 24 h after the initiation of cortisol administration. The fetuses received 0, 4.8 or 24.0 mg cortisol/24 h i.v. and umbilical blood was collected at 12 h intervals for the determination of cortisol levels. Placental microsomes prepared from the fetal cotyledons were incubated with extraction, substrates and expected main products including both estrone and estradiol were separated, identified and quantitated. The incubation of pregnenolone with ovine placental microsomes resulted in significant increases in the conversion of pregnenolone to 17.alpha.-hydroxypregnenolone with cortisol and suggested an induced placental 17.alpha.-hydroxylase enzyme. No significant differences in the conversion of 17.alpha. hydroxyprogesterone to C19-steroids could be demonstrated and no induction or activation of the steroid 17,20-lyase by cortisol was detected. The ovine placental microsomal aromatizing activities with pregnenolone or 17.alpha.-hydroxyprogesterone as substrate were not significantly different between control and cortisol-treated animals. Although cortisol has an effect on the activity of the 17.alpha.-hydroxylase, it does not raise the activity of the steroid 17,20-lyase. An increase in this activity would not appear to account for the increased synthesis of estrogens from C21-steroids.