concept

GRE (glucocorticoid response elements)

The glucocorticoid receptor (GR) [2] binds to specific DNA sequences – glucocorticoid response elements (GREs) – which may be positive or negative, either activating or repressing transcription, respectively (Fig. (Fig.1).1). In the absence of ligand, the receptor is cytoplasmic and is complexed with chaperones, including hsp90, hsp56 (immunophilin), and calreticulin. Upon ligand binding to the receptor, the chaperones are shed, exposing nuclear localisation signals. The receptor dimerises when it binds to a GRE. Genes that are positively regulated by GREs include those involved in gluconeogenesis, such as those for tyrosine aminotransferase, alanine aminotransferase, and phosphoenolpyruvate carboxykinase. Examples of genes negatively regulated by GREs are those for pro-opiomelanocortin (the ACTH precursor) and prolactin. The genes responsible for such side effects of glucocorticoids as osteoporosis, diabetes, and hypertension are largely unknown. Understanding the transcriptional basis of the different physiological effects is important because it may be possible to develop more selective agents, which target the inflammatory process.

Ref:
Saklatvala J. Glucocorticoids: do we know how they work? Arthritis Res. 2002;4(3):146-50. doi: 10.1186/ar398. Epub 2002 Jan 21. PMID: 12010562; PMCID: PMC128923.

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Added on Nov 26, 2023 by Barbara Van De Keer

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