Effects of cholestenone feeding in rats

Abstract

In several conditions (e.g. congenital lipoid adrenal hyperplasia; disorders of bile acid synthesis), sterol metabolism is disturbed and formation of abnormal sterols can be expected. In a pilot study we investigated the effects of cholestenone, a cholesterol metabolite which occurs normally in low concentrations only. Cholestenone, fed for 3½ months, (1% w/w in the standard laboratory chow) was found to cause significant growth retardation in male Wistar rats (mean weight 270 g (n=3) vs. 380 g (n=3) of controls). The adrenals were grossly enlarged (mean weight 44.4 mg vs. 19.1 mg in controls). Growth retardation also occurred in female rats fed cholestenone. Their ovaria as well as adrenals were hyperplastic and pale yellow. Isolated adrenal cells of test animals showed complete loss of sensivity for ACTH at a concentration of 100μU/ml.They were unable to synthesize corticosterone from exogenous 25-OH-cholesterol. Corticosterone production from exogenous pregnenolone dropped to 20% of control values. In the blood and other tissues cholesterol, both free and esterified, was partly replaced by cholestanol and its esters. Resistance of the erythrocytes to osmotic shock was significantly decreased.