Regulation of Placental Low Density Lipoprotein Uptake in Baboons by Estrogen*

We have previously shown that placental low density lipoprotein (LDL) uptake is decreased in baboons treated with antiestrogen and we have proposed, therefore, that estrogen regulates placental LDL uptake and use during primate pregnancy. In the present study, an alternate in vivo approach was employed to determine whether restoration of estrogen in animals in which the formation of estrogen was decreased would reverse the decline in LDL uptake. Placental estrogen was suppressed by removing the fetus (fetectomy) and thus adrenal androgens on day 100 of baboon gestation (term is 184 days). Placental LDL uptake was determined on day 160 after fetectomy alone, and after fetectomy and sc administration of the estrogen precursor androstenedione (50 to 150 mg every 10 days). Placental cells (106) were dispersed with 0.1% collagenase, isolated via 50% Percoll gradient centrifugation, then incubated at 37 C for 12 h in medium 199 with 10–100 μg [125I]LDL and LDL uptake (i.e. binding and internalization) determined by Scatchard analysis. In intact baboons and animals that had undergone fetectomy, syncytiotrophoblasts predominated and formed a continuous surface covering of the placental villi. Moreover, placental cells of intact and fetectomized baboons isolated on 50% Percoll consisted primarily of syncytiotrophoblasts, as evidenced by their immunohistochemical reaction with antisera against placental lactogen and pregnancy-specific-β1i-glycoprotein. Serum estradiol in untreated baboons increased with advancing gestation and mean (±SE) concentrations were 1.29 ± 0.04 ng/ml on days 101–160 of gestation. Placentas remained in situ and viable after fetectomy, but serum estradiol decreased to 0.24 ± 0.02 ng/ ml, or 19% of normal (P < 0.01). Androstenedione restored serum estradiol after fetectomy to a mean of 0.69 ± 0.03 ng/ml on days 101–160, or 53% of normal. Specific LDL uptake (nanograms per μg protein) by placental cells after fetectomy alone (3.2 ± 0.4) was 22% (P < 0.001) of controls (14.4 ± 1.2). Androstenedione increased (P < 0.005) LDL uptake after fetectomy to a value (8.8 ± 1.2) that was 61% of normal. LDL degradation, which depends on uptake, was 59 ± 1% of normal after fetectomy and restored with androstenedione treatment to 94 ± 2% of normal. Apparent dissociation constants (μg/ml) for LDL uptake were similar after fetectomy (0.38), and fetectomy and androstenedione treatment (0.41), but lower (P < 0.01) than in intact animals (0.80). Serum LDL concentrations on days 101-160 in controls (45.6 ± 3.0 mg/dl) were not altered by fetectomy or administration of androstenedione after fetectomy. Serum progesterone concentrations in untreated baboons were 10.0 ± 0.2 ng/ml on days 101–160 and no significant progressive rise or fall was observed. After fetectomy, serum progesterone declined to 3.3 ± 0.2 ng/ml, or 33% of normal (P < 0.01). Concentrations of progesterone after fetectomy and androstenedione were 3.7 ± 0.2 ng/ml. In summary, fetectomy resulted in a loss in estrogen formation and decrease in placental LDL uptake, and these effects were largely reversed by androstenedione. The results support the hypothesis that estrogen regulates receptor-mediated placental cell uptake of LDL during primate pregnancy. (Endocrinology128: 450–458, 1991)