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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Effect of tumor necrosis factor-α on estrogen metabolism and endometrial cells: Potential physiological and pathological relevance
Journal of Clinical Endocrinology and Metabolism, Volume 94, No. 1, Year 2009
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Description
Context: Estrogen and its metabolites play a critical role in the pathophysiology of the endometrium. The bioavailability of estrogen and estrogen metabolites in endometrial tissues depends on the expression of enzymes involved in estrogen biosynthesis and metabolism. Substantial evidence indicates that estrogen-dependent endometrial disorders are also associated with proinflammatory milieu. However, the mechanism whereby inflammation contributes to these conditions is not known. Objective: The objective of the study was to investigate the effect of TNF-α on estrogen metabolism and the expression of estrogen-metabolizing genes in human endometrial glandular epithelial cells (EM1). Design: EM1 were treated with 17β-estradiol (E2) with or without TNF-α. Capillary liquid chromatography-tandem mass spectrometry analysis was used for quantitative measurement of estrogens and estrogen metabolites. Western blot analysis, reporter gene assay, and real-time RT-PCR were used to assess the expression of estrogen-metabolizing genes. Results: TNF-α treatment significantly increased the level of total estrogen and estrogen metabolites and significantly increased the rate of conversion of estrone (E1) into E2. TNF-α also enhanced the oxidative metabolism of estrogen into catecholestrogens with concomitant inhibition of their conversion into methoxyestrogens. Gene expression analysis revealed that TNF-α induced the expression of genes involved in E2 biosynthesis (steroidogenic factor-1 and aromatase) and activation (17β-hydroxysteroid dehydrogenase type 1 and cytochrome P-450, 1B1) with simultaneous repression of genes involved in estrogen inactivation (17β-hydroxysteroid dehydrogenase type 2; catechol O-methyltransferase; and nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1). Conclusion: TNF-α increases the local estrogen biosynthesis in human endometrial glandular cells and directs estrogen metabolism into more hormonally active and carcinogenic metabolites. These effects may impact many physiological and pathological processes that occur within the endometrium. Copyright © 2009 by The Endocrine Society.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2630861/bin/jc.2008-1389_index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2630861/bin/jc.2008-1389_1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2630861/bin/jc.2008-1389_2.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2630861/bin/jc.2008-1389_3.pdf
Authors & Co-Authors
Salama, Salama Abdou
United States, Galveston
The University of Texas Medical Branch at Galveston
Egypt, Cairo
Faculty of Pharmacy
Kamel, Marwa W.
United States, Galveston
The University of Texas Medical Branch at Galveston
Egypt, Giza
Cairo University
Diaz-Arrastia, Concepcion R.
United States, Galveston
The University of Texas Medical Branch at Galveston
Xu, Xia
United States, Frederick
Saic-frederick
Veenstra, Timothy D.
United States, Frederick
Saic-frederick
Salih, Sana M.
United States, Madison
University of Wisconsin-madison
Botting, Shaleen K.
United States, Galveston
The University of Texas Medical Branch at Galveston
Kumar, Raj
United States, Galveston
The University of Texas Medical Branch at Galveston
Statistics
Citations: 63
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1210/jc.2008-1389
ISSN:
0021972X
e-ISSN:
0021972X
Research Areas
Cancer
Genetics And Genomics
Study Approach
Quantitative