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Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterusPrevious 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.
Document ID
20040112571
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Krumenacker, J. S.
(University of Texas Medical School 6431 Fannin Street, Houston, TX 77030, United States)
Hyder, S. M.
Murad, F.
Date Acquired
August 21, 2013
Publication Date
January 16, 2001
Publication Information
Publication: Proceedings of the National Academy of Sciences of the United States of America
Volume: 98
Issue: 2
ISSN: 0027-8424
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HD-08615
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cardiopulmonary

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