Genome and hormones: Gender differences in physiology - Selected contribution: Cerebrovascular NOS and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-alpha

Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-alpha knockout ( alpha ERKO) mice were used to test whether estrogen acts via ER-alpha. Mice were ovariectomized, with or without estrogen replacement, and cerebral bl ood vessels were isolated 1 mo later. Estrogen increased levels of endothel ial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mi ce but was ineffective in alpha ERKO mice. Endothelium-denuded middle cereb ral artery segments from all animals constricted when pressurized. In denud ed arteries from alpha ERKO but not wild-type mice, estrogen treatment enha nced constriction. In endothelium-intact, pressurized arteries from wild-ty pe estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethac in were greater in arteries from wild-type estrogen-treated mice compared w ith arteries from untreated wild-type mice. In contrast, estrogen treatment of alpha ERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-alpha regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effe cts of estrogen on cerebral artery reactivity.