THE THYMOLYTIC ACTIVITY OF 21-DEOXYCORTICOSTEROIDS

Abstract

A bioassay procedure utilizing the thymus weight of the immature rat as the criterion of the response was employed to estimate the potency of several 21-deoxycorticosteroids relative to cortisol. The steroids were dissolved in corn oil and administered subcutaneously in divided doses over a period of two days. Although many of the 21-deoxy derivatives were more active than cortisol, the removal of the 21-hydroxyl group always depressed the ability of the corticosteroid analogue to produce thymic involution. A reduction of 60 to 90 per cent in thymolytic activity relative to the parent corticosteroid was experienced when either a hydrogen or a fluorine atom was substituted for the hydroxyl group at C21. The magnitude of the decrease in biological effectiveness appeared to be dependent on the presence of other groups in the corticosteroid molecule. A loss of 90 to 95 per cent in relative potency was obtained when the 21-hydroxyl was replaced by either an aldehyde, a methyl, or a peperi-dino group. When the a ketol side chain at C17 of a [DELTA]4-3-keto-11-oxysteroid was exchanged for another type of grouping, the resulting compound no longer behaved like an adrenal corticosteroid in the thymus involution assay. The results of this study suggest that the biological activity of 21-deoxycorticosteroids relative to their parent steroids depends largely on the target organ used to measure the response to the compounds.