01 Nov 2001

Estrogen influences a seemingly endless list of physiological processes, among them blood circulation. Indeed, enhanced blood flow to critical areas of the brain is one candidate hypothesis for why estrogen replacement therapy appears to protect women against Alzheimer's disease. Writing in the Journal of Applied Physiology, researchers from the University of California at Irvine and the National Institute of Environmental Health Sciences shed light on the receptor mechanism that estrogen employs in dilating blood vessels.

Previous work had established that treatment with estrogen increases the diameter of cerebral blood vessels by raising levels of nitric oxide and a prostaglandin in the endothelium, the innermost layer of blood vessel walls. Sue Duckles, Greg Geary, and colleagues now report that this effect is mediated by the alpha estrogen receptor. In their study, wild-type mice responded to one month of estrogen treatment with increased production of nitric oxide synthase and cyclooxygenase-1 (COX-1), enzymes responsible for the production of the vasodilators nitric oxide and prostacyclin. Knockout mice lacking the α estrogen receptor were unable to respond to estrogen in this way.

"By identifying α-ER, we have brought this work closer to eventually identifying possible drugs that work on the receptor to increase blood flow," Duckles said. On the question of the relevance of this work to Alzheimer's, Duckles said, "There is some thought that cerebrovascular function can contribute to the progression of AD. Thus our work showing that estrogen preserves vascular function could be directly relevant. In addition, however, blood vessels produce inflammatory factors that could contribute to AD pathology. Our work shows that production of these factors is also regulated by estrogen."—Hakon Heimer