ANTAGONISTS TO CORTISONE: AN ACTH-LIKE ACTION OF STEROIDS

Abstract

The atrophy of the adrenal cortices which normally follows cortisone treatment was prevented either completely or partially by the simultaneous admn. of other steroids in immature male rats. The most effective antagonists of cortisone were a group of C-19 or C-20 steroids such as dihydrotestosterone, methy-landrostenediol, testosterone methyl ether and testosterone propionate. Less than 2 mg./day of these compounds effectively counteracted the adrenal-inhibiting effects of 1 mg./day of cortisone acetate in either 7- or 20-day treatment periods. Dehydroepiandrosterone was only weakly effective. Estradiol benzoate was partially effective at doses of 10 [mu]g./day. C-21 steroids such as the ethyl or vinyl derivatives of testosterone or androstenediol were weak or inactive. The characteristic depletion of adrenal lipid and most other histological alterations which followed cortisone treatment were prevented by those steroids which prevented adrenal atrophy. No correlation could be made between the ability of steroids to maintain the adrenal and their androgenicity, testis-inhibiting or other known biological properties. The compounds which prevented cortisone from causing adrenal atrophy had little, if any, effect on adrenal wt. or histology when given alone. Methylan-drostenediol prevented adrenal atrophy to some degree in hypophysectomized rats but less effectively than in cortisone-treated groups. Most of the steroids used counteracted to some degree the body wt. depressing effects of cortisone whether or not they maintained the adrenals.