11 beta-hydroxysteroid dehydrogenase: a link between the dysregulation of cortisol metabolism and hypertension

Endocrine pathology is a well-recognised and important cause of human hyper tension. Recent research has highlighted the role of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) in the development of certain forms of hyperte nsion. This enzyme, which exists as two genetically unique isoforms, 11 bet a-HSD1 and 11 beta-HSD2, is responsible for the interconversion of biologic ally active cortisol with its inactive 11-oxo derivative, cortisone. Congen ital deficiency of 11 beta-HDS2 results in inappropriate activation of the renal mineralocorticoid receptor by cortisol, leading to hypertension, hypo kalaemia and metabolic alkalosis. Several authors have postulated a link be tween changes in 11 beta-HSD activity and the development of certain forms of essential hypertension. The existence of endogenous inhibitors of the en zyme provides compelling evidence in favour of this hypothesis, but few hav e been able to demonstrate a clear link between inhibition of 11 beta-HSD2 activity and hypertension by this mechanism. Similarly, several authors hav e suggested a relationship between reduced placental 11 beta-HSD2 activity, low birth weight with high placental weight, and the development of hypert ension in adulthood. However, no clear evidence to suggest a direct correla tion between birth weight, placental weight and 11 beta-HSD2 activity has b een demonstrated. While the role of 11 beta-HSD in the development of hyper tension remains controversial, an understanding of the interplay of this en zyme with both mineralocorticoid and glucocorticoid receptors undoubtedly w ill yield data that will clarify this complex field.