The overall goal of the this project is to understand how cells and tissues respond to environmental stress. Glucocorticoids, a primary stress response hormone released following the activation of the hypothalamic pituitary adrenal axis. Chronic evaluation of glucocorticoids due to prolonged stress and/or chronic therapeutic intervention with glucocorticoids has numerous detrimental actions on human health and 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 in order to provide insights and discoveries concerning their actions on cell growth, differentiation and cell death. These hormones regulate numerous aspects of physiology including glucose homeostasis, protein metabolism, skeletal growth, connective tissue metabolism, respiratory function, immune surveillance and components of human behavior. This diversity of actions has made glucocorticoids attractive for therapeutic development and, as a class of compounds, they are among the most prescribed drugs in the world. They remain a primary treatment for the environmental disease, asthma, as well as a host of other inflammatory conditions in humans.

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2009
Total Cost
$2,545,319
Indirect Cost
City
State
Country
Zip Code
Quinn, Matthew A; Xu, Xiaojiang; Ronfani, Melania et al. (2018) Estrogen Deficiency Promotes Hepatic Steatosis via a Glucocorticoid Receptor-Dependent Mechanism in Mice. Cell Rep 22:2690-2701
Cain, Derek W; Cidlowski, John A (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17:233-247
Oakley, Robert H; Busillo, John M; Cidlowski, John A (2017) Cross-talk between the glucocorticoid receptor and MyoD family inhibitor domain-containing protein provides a new mechanism for generating tissue-specific responses to glucocorticoids. J Biol Chem 292:5825-5844
Whirledge, Shannon; Cidlowski, John A (2017) Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction. Trends Endocrinol Metab 28:399-415
Busada, Jonathan T; Cidlowski, John A (2017) Mechanisms of Glucocorticoid Action During Development. Curr Top Dev Biol 125:147-170
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Quinn, Matthew A; Cidlowski, John A (2016) Endogenous hepatic glucocorticoid receptor signaling coordinates sex-biased inflammatory gene expression. FASEB J 30:971-82
He, Bo; Cruz-Topete, Diana; Oakley, Robert H et al. (2016) Human Glucocorticoid Receptor ? Regulates Gluconeogenesis and Inflammation in Mouse Liver. Mol Cell Biol 36:714-30
Venturutti, L; Cordo Russo, R I; Rivas, M A et al. (2016) MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1. Oncogene 35:6189-6202
Cruz-Topete, Diana; He, Bo; Xu, Xiaojiang et al. (2016) Krüppel-Like Factor 13 is a major mediator of Glucocorticoid Receptor-Signaling in Cardiomyocytes and protects these Cells from DNA Damage and Death. J Biol Chem :

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