Comparison of the effects of some C 27−, C 21−, and C 19-steroids upon hepatic sterol synthesis and hydroxymethylglutaryl—CoA reductase activity

Abstract

Studies were undertaken to determine whether the inhibitory effects upon hepatic sterol synthesis of cholesterol and a number of structurally and metabolically related steroids could be differentiated in terms of inhibitory potency when fed or injected or in terms of their effects upon the level of HMG-CoA reductase activity. The inhibitory potencies of cholesterol, cholest-4-en-3-one, cholesta-4,6-dien-3-one, cholestanone, and cholestanol were approximately equal and were greater than those of testosterone, androsta-4,6-dien-17β-ol-3-one, and progesterone when the steroids were fed at low or moderate levels in the diet. At the highest level of administration with the diet cholest-4-en-3-one and androsta-4,6-dien-17β-ol-3-one stimulated sterol synthesis from acetate. Intraperitoneal injection of cholest-4-en-3-one, cholesta-4,6-dien-3-one, testosterone, androsta-4,6-dien-17β-ol-3-one, or progesterone depressed the rate of sterol synthesis from acetate, whereas other steroids tested were inactive under these conditions. Depression of the rate of sterol synthesis from acetate by dietary or injected steroids was uniformly associated with a diminished level of HMG-CoA reductase activity.