Placental Secretion of Androgens in the Rat*

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Abstract
In contrast to the human placenta, which does not secrete androgens, the rat placenta synthesizes significant amounts of these steroids. The purpose of this study was to determine why the rat placenta does not secrete androgens before day 12 of pregnancy, to ascertain whether the rat placenta secretes more androstenedione than testosterone, to compare the capacity of luteal and placental tissue to secrete androgen and to determine whether the rat placenta produces androstenedione via the .DELTA.4- or .DELTA.5-steroidogenic pathway. To determine whether the inability of the rat placenta to produce androstenedione before midpregnancy was due to the absence of active 17.alpha.-hydroxylase and 17,20-lyase enzymes and also to investigate the ontogeny of both placental production of androstenedione and enzyme activities, placentas were isolated from rats between days 8-21 of pregnancy and either incubated or used to determine the activities of 17.alpha.-hydroxylase and 17,20-lyase. Before day 11, enzyme activity was not detectable. From day 11, both enzyme activities and placental secretion of androstenedione steadily increased to peak values by day 18 and declined just before parturition. To investigate the principal aromatizable androgen secreted both in vivo and in vitro approaches were used. Levels of androstenedione and testosterone found in the uterine vein as well as those produced by placental tissue were determined. Rat placentas secreted markedly more androstenedione than testosterone, both in vivo and in vitro. When placental and luteal secretion of androstenedione and testosterone were compared, it was found that luteal tissue had a higher capacity for androgen synthesis than did the placenta. Yet, because of its greater mass, each placenta secreted 15 times more androstenedione and 4.5 times more testosterone than each corpus luteum. To determine the preferential usage of progesterone or pregnenolone as substrate by the placenta, [14C] progesterone and [3H]pregnenolone were added in equimolar concentrations. The resulting 14C to 3H ratio of the androgen produced indicates that the preferred substrate is progesterone. In summary, results of this investigation describe, for the first time, the development of 17.alpha.-hydroxylase and 17,20-lyase activities in the rat placenta and demonstrate that the placenta does not produce androgen before day 11 due to the absence of active enzymes. The results further demonstrate that the rat placenta secretes significantly more androstenedione than testosterone both in vivo and in vitro, produces more androgen than the corpus luteum because of its greater mass, and forms its androgen primarily via the .DELTA.4-steroidogenic pathway.