EFFECTS OF DEXAMETHASONE 17-ESTERS ON ADRENAL WEIGHT AND HYDROLYSIS OF GLUCOCORTICOID 17-ESTERS IN RAT FETUSES

Abstract

Prednisolone was detected in the brain of rat fetus subcutaneously administered prednisolone 17-acetate. After the subcutaneous injection of betamethasone 17-propionate or dexamethasone 17-propionate to rat fetus, the unchanged steroid was detected mainly in the brain. The hydrolytic rates of prednisolone 17-acetate, betamethasone 17-esters (acetate, propionate) and dexamethasone 17-esters (acetate, propionate, valerate) in the livers of rat fetuses were studied. Prednisolone 17-acetate was hydrolyzed to prednisolone very rapidly. Betamethasone 17-esters and dexamethasone 17-esters were hydrolyzed more slowly. The hydrolytic rate of dexamethasone acetate among the dexamethasone 17-esters was the most rapid, followed by propionate and valerate. The adrenals of rat fetuses became significantly atrophied after subcutaneous administration of dexamethasone and its 17-esters. The simultaneous administration of betamethasone 17, 21-dipropionate and its metabolite betamethasone impaired the hypertrophic effect of the former on the adrenal weights of rat fetuses. The effects of the hydrolytic rate of these glucocorticoid 17-esters and of C16-methyl conformation on the hypothalamo-pituitary-adrenal system in rat fetuses are discussed.