11ß-hydroxysteroid dehydrogenases: A growing multi-tasking family.
Mol Cell Endocrinol
; 526: 111210, 2021 04 15.
Article
em En
| MEDLINE
| ID: mdl-33607268
ABSTRACT
This review briefly addresses the history of the discovery and elucidation of the three cloned 11ß-hydroxysteroid dehydrogenase (11ßHSD) enzymes in the human, 11ßHSD1, 11ßHSD2 and 11ßHSD3, an NADP+-dependent dehydrogenase also called the 11ßHSD1-like dehydrogenase (11ßHSD1L), as well as evidence for yet identified 11ßHSDs. Attention is devoted to more recently described aspects of this multi-functional family. The importance of 11ßHSD substrates other than glucocorticoids including bile acids, 7-keto sterols, neurosteroids, and xenobiotics is discussed, along with examples of pathology when functions of these multi-tasking enzymes are disrupted. 11ßHSDs modulate the intracellular concentration of glucocorticoids, thereby regulating the activation of the glucocorticoid and mineralocorticoid receptors, and 7ß-27-hydroxycholesterol, an agonist of the retinoid-related orphan receptor gamma (RORγ). Key functions of this nuclear transcription factor include regulation of immune cell differentiation, cytokine production and inflammation at the cell level. 11ßHSD1 expression and/or glucocorticoid reductase activity are inappropriately increased with age and in obesity and metabolic syndrome (MetS). Potential causes for disappointing results of the clinical trials of selective inhibitors of 11ßHSD1 in the treatment of these disorders are discussed, as well as the potential for more targeted use of inhibitors of 11ßHSD1 and 11ßHSD2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
11-beta-Hidroxiesteroide Desidrogenases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article