In the present study, increasing amounts of the anti-estrogen 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenolethanol (MER-25) were administered to pregnant baboons (Papio anubis) to block the action of endogenous estrogen and to determine effect on placental low-density lipoprotein (LDL) uptake. Pregnant baboons were untreated (n = 8) or received MER-25 orally at a dosage of 25 (n = 10), 50 (n = 8), or 75 (n = 4) mg/kg BW daily on Days 140-170 of gestation (term = 184 days). Placentas were removed on Day 170 of gestation and villous tissue was dispersed with 0.1% collagenase. Placental cells (10(6)) were incubated in Medium 199 for 12 h at 37-degrees-C with increasing amounts of I-125-LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SEM) placental uptake (ng/mu-g cell protein) of I-125-LDL was 55% (6.4 +/- 1.0), 75% (3.6 +/- 0.7), and 81% (2.7 +/- 0.2) lower (p < 0.001) in baboons that received MER-25 in doses of 25, 50, and 75 mg/kg BW, respectively, than in untreated baboons (14.2 +/- 1.3 ng/mu-g cell protein). Maximal effect occurred with 50 mg MER-25, because LDL uptake was not further decreased with greater levels of MER-25. Dissociation constants for placental LDL uptake, as determined by Scatchard analysis, were unaltered by anti-estrogen treatment. The amount of I-125-LDL degradation by placental cells of untreated and MER-25-treated baboons was proportional to LDL uptake. Peripheral serum progesterone (P4) concentrations on Days 140-170 were 45% (6.1 +/- 0.2 ng/ml), 55% (5.0 +/- 0.3 ng/ml), and 58% (4.6 +/- 0.3 ng/ml) lower (p < 0.001) in baboons receiving MER-25 at 25, 50, and 75 mg/kg BW, respectively, than in untreated (11.0 +/- 0.6 ng/ml) baboons. These results indicate that anti-estrogen treatment decreased the amount of placental LDL uptake/degradation and placental P4 production in a dose-responsive manner, but did not alter receptor affinity for the lipoprotein. Because LDL uptake was decreased to 19% of normal with the estrogen receptor antagonist MER-25, we suggest that the placental LDL receptor is regulated primarily by estrogen during baboon pregnancy.
