NDLI: Effect of tumor necrosis factor-alpha on estrogen metabolism and endometrial cells: potential physiological and pathological relevance.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kamel, Marwa W. Salama, Salama A. Botting, Shaleen K. Veenstra, Timothy D. Diaz-Arrastia, Concepcion R. Xu, Xia Kumar, Raj Salih, Sana
Description	Country affiliation: United States Author Affiliation: Salama SA ( Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, 300 University Boulevard, Galveston, Texas 77555, USA. sasalama@utmb.edu)
Abstract	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-alpha on estrogen metabolism and the expression of estrogen-metabolizing genes in human endometrial glandular epithelial cells (EM1). DESIGN: EM1 were treated with 17beta-estradiol (E2) with or without TNF-alpha. 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-alpha treatment significantly increased the level of total estrogen and estrogen metabolites and significantly increased the rate of conversion of estrone (E1) into E2. TNF-alpha also enhanced the oxidative metabolism of estrogen into catecholestrogens with concomitant inhibition of their conversion into methoxyestrogens. Gene expression analysis revealed that TNF-alpha induced the expression of genes involved in E2 biosynthesis (steroidogenic factor-1 and aromatase) and activation (17beta- hydroxysteroid dehydrogenase type 1 and cytochrome P-450, 1B1) with simultaneous repression of genes involved in estrogen inactivation (17beta-hydroxysteroid dehydrogenase type 2; catechol O-methyltransferase; and nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1). CONCLUSION: TNF-alpha 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.
ISSN	0021972X
e-ISSN	19457197
DOI	10.1210/jc.2008-1389
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	1
Volume Number	94
Language	English
Publisher	Oxford University Press
Publisher Date	2009-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Endometrium Metabolism Estrogens Tumor Necrosis Factor-alpha Pharmacology Aromatase Genetics Aryl Hydrocarbon Hydroxylases Catechol O-methyltransferase Cell Line Cytochrome P-450 Cyp1a1 Cytochrome P-450 Cyp1b1 Cytochrome P-450 Enzyme System Cytology Estradiol Estradiol Dehydrogenases Gene Expression Regulation Drug Effects Nad(p)h Dehydrogenase (quinone) Steroidogenic Factor 1 Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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