Influence of cortisol and different steroidogenic pathways on estrogen synthesis by the bovine placenta

Abstract

SUMMARY The influence of cortisol on estrogen synthesis by the bovine placenta and the importance of the Δ4 and Δ5 pathway for estrogen production were investigated. For experiment 1, portions of fetal villi (200 mg) were incubated for 48 hours with 0, 10, 100, and 1,000 ng of cortisol/ml with [3H]androstenedione (3H-A) or [3H]pregnenolone (3H-P5). Villi were also incubated for 4, 28, and 52 hours with or without cortisol (500 ng/ml) and with 3H-A or 3H-P5 (experiment 2). The conversion of various [3H]steroid metabolites such as A, P5, 17α-OH-pregnenolone (17α-OH-P5), progesterone (P4), 17α-OH-P4, cholesterol (chol), and chol plus lipoprotein (500 μg/ml) into estrogen was measured during a 4-hour incubation (experiment 3). In experiment 1, cortisol increased conversion of 3H-A and 3H-P5 into estrogen by 3 to 41% and 7 to 34%, respectively, in a dose-dependent manner (P < 0.05). In experiment 2, times of incubation did not influence conversion of 3H-A into estrogen, which, however, was increased significantly (P < 0.05) over all times of incubation by administration of 500 ng of cortisol/ml. Conversion of 3H-P5 into estrogen increased over time of incubation and was stimulated by cortisol (P < 0.05). However, there was no interaction between cortisol treatment and time of incubation. In experiment 3, conversion of 3H-A, 3H-P5, and 3H-17α-OH-P5 into estrogen was greater than the conversion of the other precursors tested. Mean conversion of 3H-A, 3H-P5, 3H-17α-OH-P5, 3H-P4, 3H-17α-OH-P4, 3H-chol, and 3H-chol plus lipoprotein was 23%, 10.6%, 11.0%, 1.8%, 1.8%, 0.3% and 0.7%, respectively. Our results suggest that, in cows, the Δ5 pathway is the preferred pathway for placental estrogen synthesis and that cortisol directly stimulates estrogen production, probably by activating enzymes involved in this pathway.