Estradiol reduces F2alpha-isoprostane production in cultured human endothelial cells.
Free radical-generated F(2alpha)-isoprostanes are a group of compounds with vasoconstrictor properties. To investigate whether estradiol exerts antioxidant actions modifying F(2alpha)-isoprostane production, cultured human umbilical vein endothelial cells were exposed to estradiol and other compounds and F(2alpha)-isoprostanes were measured in culture medium. Exposure to 1 and 10 nM estradiol for 24 h reduced F(2alpha)-isoprostane production by 36 and 49%, respectively (P < 0.001 vs. control). Exposure to antiestrogens alone (ICI-182780 or EM-652) slightly reduced F(2alpha)-isoprostanes (P < 0.05 vs. control), but much less than exposure to estradiol (P < 0.05). ICI-182780 reversed the estradiol-induced reduction of F(2alpha)-isoprostane concentration (P < 0.05). Along with time-course analysis, these results suggest that estradiol effects were mediated through estrogen receptor-dependent and -independent mechanisms. Progestogens alone (progesterone or medroxyprogesterone acetate) did not modify F(2alpha)-isoprostane production at any of the tested concentrations (1, 10, and 100 nM). Progesterone completely reversed estradiol-induced reduction of F(2alpha)-isoprostane production (P < 0.05 vs. control and estradiol), but medroxyprogesterone acetate did not (P < 0.05 vs. control).
Hermenegildo
Carlos
C
Research Unit, Hospital Clinic Universitari de Valencia, Spain. carlos.hermenegildo@uv.es
García-Martínez
María Cinta
MC
Tarín
Juan J
JJ
Cano
Antonio
A
D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007231:Infant, Newborn; D028421:Isoprostanes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D017077:Culture Media, Conditioned; D004965:Estrogen Antagonists; D028421:Isoprostanes; D010880:Piperidines; D045167:Progesterone Congeners; D000077267:Fulvestrant; C012121:ritetronium; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate