Document Detail


ICI 182,780 acts as a partial agonist and antagonist of estradiol effects in specific cells of the sheep uterus.
MedLine Citation:
PMID:  11457666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We assessed the ability of ICI 182,780 (ICI) to block the estradiol (E2) responses of genes within the sheep uterus. Ovariectomized ewes in the 'ICI+E2' treatment group received a uterine infusion with 10(-7) M ICI for 14 h, an injection of 50 microg E2 6 h after the infusion started, and were hysterectomized 18 h postinjection. Other groups received only ICI or E2, or neither treatment ('Con'). Both E2 and ICI increased the wet weight of dissected endometrium: averaging 10.0+/-1.2 g for ICI+E2, ICI, and E2 groups compared to 6.8+/-0.6 g for Con. Slot blot analyses of endometrial RNA showed that estrogen receptor-alpha (ER), progesterone receptor (PR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), cyclophilin, actin and c-fos mRNAs responded to E2 treatment: the first five increased an average of 60% while the last decreased 38%. In situ hybridization identified more subtle ICI effects: agonistic up-regulation of GAPDH mRNA in superficial endometrial cells, and antagonistic down-regulation of ER and PR mRNAs in the inner layer of the myometrium. Thus, we conclude that the agonist versus antagonist effects of ICI relative to those of E2 are a function of the gene examined as well as the specific cell within the uterus.
Authors:
J A Robertson; Y Zhang; N H Ing
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  77     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-07-17     Completed Date:  2001-08-23     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  281-7     Citation Subset:  IM    
Affiliation:
Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Endometrium / drug effects,  physiology
Estradiol / agonists*,  analogs & derivatives,  pharmacology*
Estrogen Antagonists / pharmacology*
Female
Gene Expression Regulation / drug effects
In Situ Hybridization
Sheep
Uterus / cytology,  drug effects*
Chemical
Reg. No./Substance:
0/Estrogen Antagonists; 22X328QOC4/fulvestrant; 50-28-2/Estradiol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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