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)
Henson
M C
MC
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.
Pepe
G J
GJ
Albrecht
E D
ED
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D004978:Ethamoxytriphetol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics*; D010215:Papio / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011973:Receptors, LDL / Q000378:metabolism
D004967:Estrogens; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D011374:Progesterone; D004978:Ethamoxytriphetol