Regulation of placental low-density lipoprotein uptake in baboons by estrogen: dose-dependent effects of the anti-estrogen ethamoxytriphetol (MER-25).

In the present study, increasing amounts of the anti-estrogen 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenoletha nol (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 125I-LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SEM) placental uptake (ng/micrograms cell protein) of 125I-LDL was 55% (6.4 +/- 1.0), 75% (3.6 +/- 0.7), and 81% (2.7 +/- 0.2) lower (p less than 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/micrograms 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 125I-LDL degradation by placental cells of untreated and MER-25-treated baboons was proportional to LDL uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of estrogen antagonism on progesterone production in early pregnancy in the baboon (Papio cynocephalus).

These studies were designed to investigate the role of estrogen on progesterone production in early pregnancy in the baboon, when the contribution of the corpus luteum and placenta has not been established. Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels. The same study was done with the use of a different estrogen antagonist, trioxifene mesylate (5 mg/kg/day), and there was no effect on plasma progesterone, although a transient depression in plasma estradiol was evident. These actions may be due to an inherent estrogenicity of trioxifene. In preliminary studies an effect of these estrogen antagonists on placental size and morphology has been observed. Estrogen deprivation in early pregnancy of the baboon results in a depression in plasma progesterone and indicates a placental requirement for estrogen in progesterone product at this stage of pregnancy.