the glucocorticoid receptor a revisited target for toxins糖皮质激素受体的重新审视目标毒素.pdf

Toxins 2010, 2, 1357-1380; doi:10.3390/toxins2061357 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review The Glucocorticoid Receptor: A Revisited Target for Toxins Jeanette I. Webster Marketon 1,2,* and Esther M. Sternberg 3 1 Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care Sleep Medicine, 201 DHLRI, 473 W. 12th Avenue, Columbus, OH 43210, USA 2 Institute for Behavioral Medicine Research, The Ohio State University Medical Center, 460 Medical Center Drive, Columbus, OH 43210, USA 3 Department of Health and Human Services, Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, 5625 Fishers Lane, Rm. 4N13 (MSC 9401), Bethesda, MD 20892-9401, USA; E-Mail: sternbee@ * Author to whom correspondence should be addressed; E-Mail: jeanette.marketon@ ; Tel.: +1-614-293-3496; Fax: +1-614-366-2074. Received: 15 May 2010, in revised form: 28 May 2010 / Accepted: 7 June 2010 / Published: 9 June 2010 Abstract: The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many disea