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

TLDR

Mineralocorticoid and glucocorticoid hormones trigger distinct physiological responses, yet their receptors bind and activate transcription similarly at a consensus hormone response element. The study analyzes GR and MR activities at the plfG composite response element, where both receptors and AP1 can bind. Using MR‑GR chimeras, the authors identified that the GR N‑terminal region (aa 105–440) is required for repression of AP1‑stimulated transcription at plfG. GR represses AP1‑stimulated transcription at plfG while MR is inactive, suggesting that differential interactions of nonreceptor factors with receptor domains at composite response elements underlie their distinct physiological effects.

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.