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-Estradiol decreases hypoxic induction of erythropoietin
gene expression
Vascular Physiology Group, Department of Cell Biology and Physiology, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico 87131-5218
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 17
-estradiol (E2-) inhibits this effect. We
hypothesized that E2- decreases EPO gene expression during hypoxia.
Because E2- can induce nitric oxide (NO) production and NO can
attenuate EPO synthesis, we further hypothesized that E2- inhibition
of EPO gene expression is mediated by NO. These hypotheses were tested
in OVX catheterized rats treated with E2- (20 µg/day) or vehicle
for 14 days and exposed to 8 or 12 h of hypoxia (12%
O2) or normoxia. We found that E2- treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2- treatment did not induce endothelial NO synthase (eNOS)
expression in the kidney but potentiated hypoxia-induced increases in
plasma nitrates. We conclude that E2- decreases hypoxic induction of
EPO. However, this effect does not appear to be related to changes in
renal eNOS expression.
nitric oxide; polycythemia; hypoxia
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