Adrenal hypertrophy produced by 17alpha-esterified glucocorticoids in rat foetus

Glucocorticoids were injected sc into rat foetuses through the uterine wall on day 19 of intrauterine development; two days later the foetuses were removed and their adrenal glands were weighed. Some betamethasone derivatives produced marked adrenal hypertrophy in the foetuses. Structural characteristics of the effective compounds were 17alpha-esterification and 16beta-methylation. 9alpha-Halogenation and 21-esterification of glucocorticoids were not essential for producing the hypertrophy. Propionic acid at the C-17 position was more effective than valeric and acetic acids in producing the hypertrophy. The effect of betamethasone 17, 21-dipropionate was dose-responsive and prevented by simultaneous administration of betamethasone 21-disodium phosphate. Results obtained with decapitated or encephalectomized foetuses suggested that the hypertrophy produced was not due to a direct action of the glucocorticoids on the adrenal gland, but mediated by the hypothalamo-pituitary system.