UTILIZATION OF MATERNAL AND FETAL ANDROSTENEDIONE FOR PLACENTAL ESTROGEN PRODUCTION AT MID AND LATE BABOON PREGNANCY

The present study determined the placental and whole-body metabolism of androstenedione originating in the maternal and fetal compartments of the pregnant baboon at mid (day 100; n = 4) and late (day 165; n = 3) gestation (term = day 184) in untreated animals and at midgestation in animals (n = 3) treated with pellets (50 mg) of androstenedione inserted at 8-day intervals in the mother between days 70 and 100 of gestation. Baboons were anesthetized with ketamine-halothane-nitrous oxide, blood samples obtained from maternal, uterine, fetal and umbilical vessels during constant infusion of [H-3] or [C-14]androstenedione via the fetal or maternal circulation, respectively, and radiolabeled precursor/products in plasma purified by HPLC. The metabolic clearance rate (MCR; 1/day/kg body wt) of androstenedione in the mother was similar at mid (81 +/- 6) and late (69 +/- 12) gestation and was unaltered by treatment with androstenedione (92 +/- 17). Fetal MCR of androstenedione was 3-fold greater (P < 0.05) than in the mother and was similar in the three treatment groups. In the maternal compartment. the conversion ratio of androstenedione to estradiol (range 26-37%) exceeded (P < 0.05) that to testosterone (range 15-19%) which exceeded (P < 0.05) that to estrone (range 7-14%), a pattern unaffected by stage of gestation or treatment with androstenedione in vivo. Similar results were observed in the fetal compartment although values for each conversion were always 3-4-fold lower (P < 0.05) than in the maternal compartment. Regardless of stage of gestation or treatment with androstenedione, [C-14]estradiol in the uterine vein (95 +/- 15 cpm/ml) exceeded (P < 0.05) that in the umbilical vein (3 +/- 1) indicative of preferential secretion of estradiol to the maternal compartment. In contrast, the concentration of [C-14]estrone in uterine (15 +/- 4) and umbilical (18 +/- 4) vessels were similar indicating that estrone was secreted equally into the mother and fetus. Similar observations were noted for respective values for [H-3]estrogens derived from fetal [H-3]androstenedione. Placental extraction of fetal androstenedione (range 86-93%) exceeded (P < 0.05) that for androstenedione originating in the mother (range 44-54%) and neither were affected by stage of gestation or treatment with androstenedione in vivo. Less than 1% of fetal [H-3]androstenedione reached the maternal circulation unaltered, presumably due to placental catabolism. Similarly, the concentration of maternally-derived [C-14]androstenedione present in fetal plasma (< 5%) was minimal. We conclude that both maternal and fetal androstenedione were extracted by the uterus and its contents and utilized almost equally for estrogen synthesis during the second half of gestation in the baboon.