17Beta-estradiol decreases hypoxic induction of erythropoietin gene expression.
Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17beta-estradiol (E2-beta) inhibits this effect. We hypothesized that E2-beta decreases EPO gene expression during hypoxia. Because E2-beta can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-beta inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-beta (20 microg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O(2)) or normoxia. We found that E2-beta treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-beta treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-beta decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.
Mukundan
Harshini
H
Vascular Physiology Group, Department of Cell Biology and Physiology, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico 87131-5218, USA. hmukundan@salud.unm.edu
Resta
Thomas C
TC
Kanagy
Nancy L
NL
D000818:Animals; D001784:Blood Gas Analysis; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006400:Hematocrit; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014599:Uterus / Q000187:drug effects
D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D004921:Erythropoietin; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat