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  • Title: Glucocorticoids and 11β-hydroxysteroid dehydrogenases: mechanisms for hypertension.
    Author: Hunter RW, Bailey MA.
    Journal: Curr Opin Pharmacol; 2015 Apr; 21():105-14. PubMed ID: 25666420.
    Abstract:
    Glucocorticoid excess induces hypertension, in which abnormal renal sodium homeostasis is implicated. It is common in industrialised nations where hypertension remains the major risk-factor for cardiovascular disease. Aldosterone is the dominant chronic regulator in sodium homeostasis, but glucocorticoids influence renal sodium transport through mineralocorticoid and glucocorticoid receptor activation, particularly in disease. Here we focus on the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine, paracrine and endocrine control over glucocorticoid signalling. Both 11βHSD1 and 11βHSD2 influence circulating glucocorticoid levels. Inappropriately high 11βHSD1 activity in the renal medulla causes systemic hypertension; the molecular mechanism is not known. The deactivation of glucocorticoid by 11βHSD2 controls ligand access to glucocorticoid and mineralocorticoid receptors; loss of function promotes salt retention and hypertension.
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