Glucocorticoid receptor and heat shock factor 1: novel mechanism of reciprocal regulation.
Glucocorticoids control a host of bodily responses, ranging from carbohydrate metabolism in the liver to immunity and inflammation in the lymph system. In response to stress, glucocorticoid levels are known to rise-a response thought to provide a protective function against the stress event. It is now understood that the major function of glucocorticoids under stress is to protect not against the stress event itself but against overstimulation by host defenses (e.g., inflammation). Control of these responses is achieved by the glucocorticoid receptor, a member of the steroid receptor transcription factor family. The oldest, most conserved, and most ubiquitous of the stress responses is induced expression of heat shock proteins that act as chaperones against stress-induced denaturation of protein. Expression of heat shock protein genes is controlled by heat shock transcription factor 1. In this work, we review our observations and those of other laboratories demonstrating a relationship between the glucocorticoid and heat shock responses. We show that complex but reciprocal mechanisms of regulation occur between glucocorticoid receptor and heat shock transcription factor 1 and present a model of coordinated action that likely serves to fully reestablish homeostasis following stress.
Li
Dapei
D
Department of Pharmacology, Medical College of Ohio, Toledo, Ohio 43614, USA.
Sánchez
Edwin R
ER
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors