Minireview: new molecular mediators of glucocorticoid receptor activity in metabolic tissues.
The glucocorticoid receptor (GR) was one of the first nuclear hormone receptors cloned and represents one of the most effective drug targets available today for the treatment of severe inflammation. The physiologic consequences of endogenous or exogenous glucocorticoid excess are well established and include hyperglycemia, insulin resistance, fatty liver, obesity, and muscle wasting. However, at the molecular and tissue-specific level, there are still many unknown protein mediators of glucocorticoid response and thus, much remains to be uncovered that will help determine whether activation of the GR can be tailored to improve therapeutic efficacy while minimizing unwanted side effects. This review summarizes recent discoveries of tissue-selective modulators of glucocorticoid signaling that are important in mediating the unwanted side effects of therapeutic glucocorticoid use, emphasizing the downstream molecular effects of GR activation in the liver, adipose tissue, muscle, and pancreas.
Department of Pharmaceutical Sciences (R.P., J.W-D., C.L.C.), University of Toronto, Toronto, Ontario, M5S 3M2, Canada; and Banting and Best Diabetes Centre (C.L.C.), Toronto, Ontario M5G 2C4 Canada.
Rucha
R
Patel
Jasmine
J
Williams-Dautovich
Carolyn L
CL
Cummins
D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D050155:Lipogenesis / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D005938:Glucocorticoids; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid