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J Appl Physiol (June 22, 2006). doi:10.1152/japplphysiol.01095.2005
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Submitted on September 6, 2005
Accepted on June 6, 2006

The influence of sex steroid hormones on cerebrovascular function

Diana N. Krause1*, Sue Piper Duckles1, and Dale A. Pelligrino2

1 Pharmacology, University of California, Irvine, Irvine, California, United States
2 Neuroanesthesia Research Laboratory, University of Illinois at Chicago, Chicago, Illinois, United States

* To whom correspondence should be addressed. E-mail: dnkrause{at}uci.edu.

The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens, androgens and progestins all influence the function and pathophysiology of the cerebral circulation. Estrogen decreases cerebral vascular tone and increases cerebral blood flow by enhancing endothelial-derived nitric oxide and prostacyclin pathways. Testosterone has opposite effects, increasing cerebral artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased by testosterone and progesterone. Evidence suggests sex steroids also modulate blood-brain barrier permeability. Estrogen has important protective effects on cerebral endothelial cells by increasing mitochondrial efficiency, decreasing free radical production, promoting cell survival and stimulating angiogenesis. While much has been learned regarding hormonal effects on brain blood vessels, most studies involve young, healthy animals. It is becoming apparent that hormonal effects may be modified by aging or disease states such as diabetes. Furthermore, effects of testosterone are complicated since this steroid is also converted to estrogen, systemically and possibly within the vessels themselves. Elucidating the impact of sex steroids on the cerebral vasculature is important for understanding male-female differences in stroke and conditions such as menstrual migraine and pre-eclampsia-related cerebral edema in pregnancy. Cerebrovascular effects of sex steroids also need to be considered in untangling current controversies regarding consequences of hormone replacement therapies and steroid abuse.




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