The overall goal of the this project is to understand how cells and tissues respond to environmental stress. Glucocorticoids are primary stress response hormones and chronic evaluation of glucocorticoids due to prolonged stress and/or chronic therapeutic intervention can lead to detrimental actions on human health. Thus studying their actions and signaling pathways is critical to the mission of NIEHS. We seek to understand how glucocorticoids signal in a cell specific manner. These hormones regulate multiple aspects of physiology including glucose homeostasis, protein metabolism, skeletal growth, connective tissue metabolism, respiratory function, immune surveillance and components of human behavior. They are essential for life in man.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$2,459,557
Indirect Cost
City
State
Country
Zip Code
Ramamoorthy, Sivapriya; Cidlowski, John A (2013) Exploring the molecular mechanisms of glucocorticoid receptor action from sensitivity to resistance. Endocr Dev 24:41-56
Whirledge, Shannon; Cidlowski, John A (2013) Estradiol antagonism of glucocorticoid-induced GILZ expression in human uterine epithelial cells and murine uterus. Endocrinology 154:499-510
Ramamoorthy, Sivapriya; Cidlowski, John A (2013) Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements. Mol Cell Biol 33:1711-22
Busillo, John M; Cidlowski, John A (2013) The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab 24:109-19
Whirledge, Shannon; Xu, Xiaojiang; Cidlowski, John A (2013) Global Gene Expression Analysis in Human Uterine Epithelial Cells Defines New Targets of Glucocorticoid and Estradiol Antagonism. Biol Reprod :
Gross, Katherine L; Lu, Nick Z; Cidlowski, John A (2009) Molecular mechanisms regulating glucocorticoid sensitivity and resistance. Mol Cell Endocrinol 300:7-16
Galliher-Beckley, Amy Jo; Williams, Jason Grant; Collins, Jennifer Brady et al. (2008) Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles. Mol Cell Biol 28:7309-22
Zhou, Junguo; Oakley, Robert H; Cidlowski, John A (2008) DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) selectively inhibits transactivation but not transrepression mediated by the glucocorticoid receptor in a LXXLL-dependent manner. Mol Endocrinol 22:1521-34
Gross, Katherine L; Cidlowski, John A (2008) Tissue-specific glucocorticoid action: a family affair. Trends Endocrinol Metab 19:331-9