The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

Abstract

Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor activation, and, in particular, the relationship between steroid hormone structure and function remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak mineralocorticoid, while the addition of an 11β-hydroxyl group produces glucocorticoid activity, yet further hydroxylation at C18 leads to the most potent mineralocorticoid, aldosterone? This review aims to show that the field has been confused by the misreading of the earlier literature and that DOC, far from being relatively inactive, in fact has a wide range of activities not shared by the other corticoids. In contrast to the accepted view, the presence of an 11β-hydroxyl group yields, in corticosterone or cortisol, hormones with more limited functions, and also more readily regulated, by 11β-hydroxysteroid dehydrogenase. This interpretation leads to a more systematic understanding of structure–function relationships in the corticosteroids and may assist more rational drug design.