NDLI: Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus.

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Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus.

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Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Murad, F. Krumenacker, J. S. Hyder, S. M.
Description	Author Affiliation: Krumenacker JS ( Department of Integrative Biology, Institute of Molecular Medicine, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030, USA.);
Abstract	Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	2
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Estradiol Analogs & Derivatives Pharmacology Guanylate Cyclase Biosynthesis Signal Transduction Drug Effects Uterus Animals Cyclic GMP Physiology Cytosol Metabolism Depression, Chemical Dimerization Enzyme Induction Estrogen Antagonists Gene Expression Regulation Chemistry Genetics Hyperemia Nitric Oxide Organ Culture Techniques Protein Isoforms Protein Subunits Protein Synthesis Inhibitors Puromycin RNA, Messenger Rats, Sprague-Dawley Receptors, Estrogen Solubility Enzymology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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