Alteration of Adrenocortical Steroidogenesis in the Rat by Inhibition of Cholesterol Biosynthesis

Oral administration of the cholesterol biosynthesis inhibitor AY-9944 [trans-1,4- bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride] did not affect the steroidogenic response to injected ACTH in hypophysectomized rats nor to laparotomy stress in normal rats 1 and 4 hr after dosage. After 7 days of treatment, serum cholesterol was lowered and partly replaced by 7-dehydrocholesterol; adrenal hypertrophy and elevated levels of adrenal and serum corticosterone were observed. Following treatment for 30 days, serum cholesterol wasfurther reduced, the adrenals were enlarged to a greater extent, and the steroidogenic response to laparotomy was impaired. Addition of cholesterol to the diet during treatment with AY-9944 prevented adrenal hypertrophy and dysfunction. In rats treated with AY-9944 for 30 days, feeding cholesterol 16 hr prior to stress restored normal steroidogenic response to laparotomy. Serum sterols and adrenal changes produced by 30 days of AY-9944 administration returned to near-normal values after 20 days of recovery. (Endocrinology83: 555, 1968)