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in cerebral blood
vessels: regulation by estrogen
Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697-4625
The cerebral vasculature is an important
target tissue for estrogen, as evidenced by significant effects of
estrogen on vascular reactivity and protein levels of 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-
(ER-) in female rat cerebral
blood vessels and localized this receptor to both smooth muscle and
endothelial cells by use of immunohistochemistry and confocal
microscopy. With immunoblot analysis, multiple forms of ER- were
detected at 110, 93, 82, 50, and 45 kDa in addition to a relatively
weak band corresponding to the 66-kDa putative unmodified receptor. The
82-kDa band was identified as Ser118-phosphorylated ER-,
whereas the 50-kDa band lacks the normal NH2 terminus,
suggestive of an ER- splice variant. Lower molecular mass bands
persisted after in vivo inhibition of 26S proteasome activity with
lactacystin, whereas the 110- and 93-kDa bands increased. All forms of
ER- in cerebral vessels were decreased after ovariectomy but
significantly increased after chronic estrogen exposure in vivo.
estrogen receptors; 26S proteasome; 17
-estradiol; cerebral
circulation
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