Inhibition of Adrenal Cortical Secretion by Amino-glutethimide in Dogs1

The acute effect of intravenous administration of amino-glutethimide (25, 50, 75 mg/kg of body wt) on adrenal venous plasma 17-hydroxycorticoid secretion has been studied i n the dog. In spite of a continuous ACTH infusion, each injection of amino-glutethimide produced a prompt fall in the secretion of 17-hydroxycorticoids. Control values were not regained 21/2 hr following amino-glutethimide. Fractionation of the adrenal venous plasma samples for individual steroids after amino-glutethimide administration revealed a decrease in cortisol and corticosterone with no detectable pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hy-droxyprogesterone, dehydroepiandrosterone, de-oxycorticosterone, and substance S. These observations, along with previous findings of increased adrenal cholesterol and lipid content, are in keeping with the view that amino-glutethimide interferes with the conversion of cholesterol to pregnenolone in the dog. (Endocrinology83: 56, 1968)