Utilization of Circulating Androstenedione and Testosterone for Estradiol Production during Gestation in the Rat1

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Abstract
The placenta provides androgen precursors for ovarian estradiol (E2) production during the second half of gestation in the rat. However, no studies have measured E2 synthesis in vivo from circulating testosterone (T) or androstenedione (A) before or after Day 12 of gestation. In addition, it is not known whether the placenta near term continues to serve as the major source of androgens. Therefore, we measured the ovarian conversion of circulating T and A to E2 in vivo on Days 11, 16, and 21 of gestation (term = Day 23). Rats (N = 6-8/group) were anesthetized with pentobarbital and a constant infusion of [3H]T or [3H]A initiated via a jugular vein. After isotopic equilibrium was achieved at 60 min, blood samples were obtained from the contralateral jugular (J) vein and a uterine-ovarian (UO) vein, and the ovaries were removed. In a second group of rats on Day 16 of gestation, either the gravid uterus or both ovaries were removed after initiation of isotope infusion, and blood samples obtained 60 min later. Radiolabeled T, A, and E2 were isolated and purified by sequential paper chromatography. The concentration of [3H]E2 following infusion of either androgen was greater in the UO vein than in the J vein on Days 16 and 21 (p<0.01), but not on Day 11, of gestation. In animals infused with [3H]T, [3H]E2 (cpm/ml) in UO vein increased (p<0.001) from 84 .+-. 33 (mean .+-. SE) on Day 11 to 357 .+-. 30 and 312 .+-. 46 on Days 16 and 21, respectively. The UO vein serum concentration of [3H]E2 following infusion of [3H]A was greater (p<0.001) on Day 16 (903 .+-. 84) than on either Day 11 (245 .+-. 84) on Day 21 (392 .+-. 60) of gestation. Acute ovariectomy, but not hysterectomy, decreased (p<0.01) the [3H]E2 concentration of UO vein serum in rats infused with either radiolabeled T or A on Day 16 of gestation. In rats infused with [3H]A, [3H]E2 in the UO vein on days 11 and 16 olf pregnancy exceeded (p<0.05) than in animals infused with [3H]T. The concentrations of [3H]E2 in ovarian tissue paralleled those measured in the UO vein. We conclude that there is significant conversion of circulating androgens to E2 by the ovary after Day 11 of gestation in the rat. Moreover, we suggest that A is the preferred circulating substrate for ovarian aromatization. The finding that circulating A and T were still utilized for E2 production on Day 21 suggests that, despite increased follicular androgen production at this time in gestation, placental androgen may continue to serve as substrate for ovarian estrogen production.