The estrogen receptor (ER) is activated and degraded by estrogen. We have examined ER downregulation and activation under hypoxia mimetic conditions. Cobalt chloride induced ER downregulation at 24 h of treatment. This degradation involved hypoxia-inducible factor-1$alpha$ (HIF-1$alpha$) as examined by using a constitutively active form of HIF-1$alpha$, HIF-1$alpha$/VP16, constructed by replacing the transactivation domain of HIF-1$alpha$ with that of VP16. Western blot analysis revealed that E2-induced ER downregulation was observed within ${~}6h$, whereas HIF-1$alpha$/VP16-induced ER degradation was observed within 12${~}$20h. HIF-1$alpha$/VP16 activated the transcription of estrogen-responsive reporter gene in the absence of estrogen. These results suggest that ER downregulation and activation under hypoxia maybe mediated in part by a HIP-1$alpha$ expression.