Mineralocorticoid and Glucocorticoid Receptor Activities Distinguished by Nonreceptor Factors at a Composite Response Element

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Abstract
Mineralocorticoid and glucocorticoid hormones elicit distinct physiologic responses, yet the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) bind to and activate transcription similarly from a consensus simple hormone response element (HRE). The activities of GR and MR at plfG, a 25-base pair composite response element to which both the steroid receptors and transcription factor AP1 can bind, are analyzed here. Under conditions in which GR represses AP1-stimulated transcription from plfG, MR was inactive. With the use of MR-GR chimeras, a segment of the NH2-terminal region of GR (amino acids 105 to 440) was shown to be required for this repression. Thus, the distinct physiologic effects mediated by MR and GR may be determined by differential interactions of nonreceptor factors with specific receptor domains at composite response elements.