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: Investigate the effect of the tumor necrosis factor(TNF) on estrogen metabolism and on the expression of estrogen-metabolizing genes in human endometrial glandular epithelial cells (EM1). Design: EM1 were treated with 17 -estradiol (E2) with or without TNF. 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: TNFtreatment significantly increased the level of total estrogen and estrogen metabolites and significantly increased the rate of conversion of estrone (E1) into E2. TNFalso enhanced the oxidative metabolism of estrogen into catecholestrogens with concomitant inhibition of their conversion into methoxyestrogens. Gene expression analysis revealed that TNFinduced the expression of genes involved in E2 biosynthesis (SF-1 and CYP19) and activation (HSD17B1 and CYP1B1) with simultaneous repression of genes involved in estrogen inactivation (HSD17B2; COMT; and NQO1). Conclusion: TNFincreases 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 endometrium. Glucocorticoid Receptor Gene Variant in the 3 Untranslated Region Is Associated with Multiple Measures of Blood Pressure Charles C. Chung, Lawrence Shimmin, Sivamani Natarajan, Craig L. Hanis, Eric Boerwinkle, and James E. Hixson (J. Clin. Endocrinol. Metab., published October 14, 2008, 10.1210/jc.2008-1089) ABSTRACT Context: The glucocorticoid receptor (GR) is a key hormone in the hypothalamus-pituitary-adrenal axis that regulates many pathways including blood pressure homeostasis. Thus, GR gene variation may influence interindividual differences in blood pressure in human populations. Objective: We resequenced individual GR alleles for comprehensive discovery of GR variants and their chromosomal phase in three major American ethnic groups. We examined the influence of GR variants on blood pressure in large numbers of families using family-based association methods. Design and Participants: For association studies, we genotyped GR variants in family members from the GENOA study that were measured for multiple blood pressure traits. The GENOA families consisted of African Americans, Mexican Americans, and European Americans. Main Measurements: The blood pressure measurements for association studies included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). T R A N S L A T I O N A L H I G H L I G H T S F R O M J C E MContext: The glucocorticoid receptor (GR) is a key hormone in the hypothalamus-pituitary-adrenal axis that regulates many pathways including blood pressure homeostasis. Thus, GR gene variation may influence interindividual differences in blood pressure in human populations. Objective: We resequenced individual GR alleles for comprehensive discovery of GR variants and their chromosomal phase in three major American ethnic groups. We examined the influence of GR variants on blood pressure in large numbers of families using family-based association methods. Design and Participants: For association studies, we genotyped GR variants in family members from the GENOA study that were measured for multiple blood pressure traits. The GENOA families consisted of African Americans, Mexican Americans, and European Americans. Main Measurements: The blood pressure measurements for association studies included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). T R A N S L A T I O N A L H I G H L I G H T S F R O M J C E M