Hydrocortisone modulates the effect of estradiol on endothelial nitric oxide synthase expression in human endothelial cells.
The interaction between hydrocortisone and estradiol on the regulation of endothelial nitric oxide synthase (eNOS) expression was investigated in human umbilical vein endothelial cells (HUVECs). Following incubation in medium containing dextran-coated-charcoal-stripped serum (DCC-stripped medium) for 4 days, incubation of HUVECs with 0.1 nM estradiol for 24 hr in the absence of hydrocortisone increased levels of eNOS mRNA measured by ribonuclease protection assay above control (0 nM estradiol). 2 microM hydrocortisone applied for 24 hr preceding and during estradiol application inhibited the estradiol-elicited increase in eNOS mRNA levels, reducing mRNA levels from 134% +/- 14% of control to 85% +/- 5% of control. Significant (ANOVA, p<0.01) reductions of estradiol-mediated increases of mRNA levels occurred over a range of hydrocortisone concentrations (10 nM, p<0.05; 2 microM, p<0.05; n=3-12). In the presence of 2 microM hydrocortisone, 10 nM estradiol significantly reduced eNOS mRNA levels to 59% +/- 3% of control. The ability of hydrocortisone to block or reverse the estradiol-mediated increase in eNOS mRNA levels may provide a link between elevated hydrocortisone levels and decreased NO production, potentially contributing to the development of hypertension and cardiovascular disease in vivo and antagonizing cardioprotective effects of estrogens.
Xu
R
R
Department of Physiology, Wayne State University, Detroit, MI 48201, USA.
Sowers
J R
JR
Skafar
D F
DF
Ram
J L
JL
D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation
D012333:RNA, Messenger; D004958:Estradiol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006854:Hydrocortisone