Glucocorticoid and Mineralocorticoid Receptors in the Brain: A Transcriptional Perspective
| Autor: | Lisa T C M van Weert, Jacobus C. Buurstede, Onno C. Meijer, Anne-Sophie C A M Koning |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
NeuroD Endocrinology Diabetes and Metabolism Context (language use) adaptation Biology Mini-Review Chromatin Cell biology 03 medical and health sciences stress 030104 developmental biology 0302 clinical medicine Glucocorticoid receptor Nuclear Receptors and Their Ligands Nuclear receptor medicine chromatin nuclear receptor DNA binding Receptor Transcription factor 030217 neurology & neurosurgery Glucocorticoid medicine.drug |
| Zdroj: | Journal of the Endocrine Society |
| Popis: | Adrenal glucocorticoid hormones are crucial for maintenance of homeostasis and adaptation to stress. They act via the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs)—members of the family of nuclear receptors. MRs and GRs can mediate distinct, sometimes opposite, effects of glucocorticoids. Both receptor types can mediate nongenomic steroid effects, but they are best understood as ligand-activated transcription factors. MR and GR protein structure is similar; the receptors can form heterodimers on the DNA at glucocorticoid response elements (GREs), and they share a number of target genes. The transcriptional basis for opposite effects on cellular physiology remains largely unknown, in particular with respect to MR-selective gene transcription. In this review, we discuss proven and potential mechanisms of transcriptional specificity for MRs and GRs. These include unique GR binding to “negative GREs,” direct binding to other transcription factors, and binding to specific DNA sequences in conjunction with other transcription factors, as is the case for MRs and NeuroD proteins in the brain. MR- and GR-specific effects may also depend on specific interactions with transcriptional coregulators, downstream mediators of transcriptional receptor activity. Current data suggest that the relative importance of these mechanisms depends on the tissue and physiological context. Insight into these processes may not only allow a better understanding of homeostatic regulation but also the development of drugs that target specific aspects of disease. |
| Databáze: | OpenAIRE |
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