17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages.
OBJECTIVE
We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture.


METHODS
Primary tissue culture of human term placental cells was performed.


RESULTS
Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations.


CONCLUSIONS
Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.
Zhu
X D
XD
Northwest Lipid Research Clinic, Department of Medicine, University of Washington School of Medicine, Seattle 98104, USA.
Bonet
B
B
Knopp
R H
RH
D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000032:analysis / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol