The development of placental androstenedione and testosterone production and their utilization by the ovary for aromatization to estrogen during rat pregnancy

Abstract

During rat pregnancy the placenta may provide androgens as a source of precursor for estradiol (E2) formation by the ovary. However, the relative importance of testosterone (T) and Δ4-androstenedione (Δ4A) for ovarian E2 production is unknown. The present study therefore determined the ability of the rat placenta to convert [3H] pregnenolone (P5) substrate to [3H]Δ4A and [3H]T, and to [3H]progesterone (P4) in vitro on Days 12, 14, 16, and 18 of gestation. The placenta formation of Δ4A and T was correlated with the uterine vein and peripheral sera concentrations of both androgens, and with their ability to be aromatized to E2 in vitro by the ovary. Placental androgen formation from P5 increased and formation of P4 decreased with advancing gestation, with the formation of Δ4A being approximately 2- to 4-fold greater (P<0.001) from 18 ± 0.9 (mean percent conversion ± SEM) on Day 12 to 53 ± 3 and 57 ± 4 on Days 14 and 16, respectively, then decreased (P<0.05) to 42 ± 2 on Day 18. The uterine vein and peripheral sera concentrations of Δ4A were 2- and 3-fold greater (P<0.05-0.001) than T, respectively, on Days 12 to 16. The ovarian percentage conversion of [3H]Δ4A to [3H]E2 was 2- to 4-fold greater (P<0.001) than the conversion from [3H]T during the second half of pregnancy. Moreover, there was a progressive increase (P<0.001) in the ability of the ovary to aromatize both Δ4A and T from Day 12 to Day 16 of gestation. The data indicate that there is a shift in placental steroidogenesis from P4 at midgestation to androgens, primarily Δ4A, during the second half of rat pregnancy. Furthermore, Δ4A appears to be produced within the placenta and secreted into the uterine venous circulation in greater quantity than T and is used preferentially by the ovary for E4 formation. We suggest, therefore, that placental Δ4A may be the predominant androgen for ovarian E2 production during the second half of rat pregnancy.