The Effect of Corticosteroid Analogues on the Thymus Gland of the Immature Rat

Abstract

The thymolytic activity of hydrocortisone (cortisol) was increased approximately 9-fold by the introduction of a fluorine atom at either the 6α- or the 9α-position. The substitution of a methyl group in the α-position at carbons 2, 6 or 16, with one exception, enhanced the ability of the corticosteroid to involute the thymus gland 3- to 4-fold. The only exception was noted when a methyl group at carbon 2 failed to increase the potency of fludrocortisone (9α-fluorohydrocortisone acetate). The formation of a double bond at the 5,6-position of the steroid molecule consistently decreased the thymolytic activity. Although the addition of an hydroxyl group in the α-position at carbon 16 decreased the relative potency of the corticosteroids, the formation of the 16α, 17α-acetonide derivative markedly enhanced it.