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Am J Physiol Endocrinol Metab (September 11, 2002). doi:10.1152/ajpendo.00165.2002
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Articles in PresS, published online ahead of print September 10, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00165.2002
Submitted on April 18, 2002
Accepted on September 4, 2002

Multiple forms of estrogen receptor-{alpha} in cerebral blood vessels: Regulation by estrogen

Chris Stirone1, Sue P. Duckles1, and Diana N. Krause1*

1 Department of Pharmacology, University of California, Irvine, Irvine, CA, USA

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

The cerebral vasculature is an important target tissue for estrogen, as evidenced by significant effects of estrogen on vascular reactivity and protein levels endothelial nitric oxide synthase and prostacyclin synthase. However, the presence, localization and regulation of estrogen receptors in the cerebral vasculature have not been investigated. In this study, we identified the presence of estrogen receptor-{alpha} (ER{alpha}) in female rat cerebral blood vessels and localized this receptor to both smooth muscle and endothelial cells using immunohistochemistry and confocal microscopy. Using immunoblot analysis, mulitple forms of ER{alpha} were detected at 110, 93, 82, 50 and 45 kDa in addition to the 66kDa putative unmodified receptor. The 82kDa band was identified as Ser-118 phosphorylated ER{alpha}, while the 50kDa band lacks the normal N-terminus, suggestive of an ER{alpha} splice variant. Lower molecular bands persisted after in vivo inhibition of 26S proteasome activity with lactacystin, while the 110 and 93 kDa bands increased. All forms of ER{alpha} were decreased after ovariectomy but significantly increased after chronic estrogen exposure in vivo.




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