Abstract
CELLS growing in a chemically defined, sterol-free medium must synthesise cholesterol or, in the case of L cells, desmosterol1 for membrane formation. Studies by others showed that when cholesterol or desmosterol was added to L-cell cultures the exogenous sterol was utilised and the rate of sterol synthesis was diminished, presumably by a negative feedback mechanism2,3. Our observations4, however, provide new information regarding the structures of sterols that affect sterol synthesis. Exogenous cholesterol and various metabolically related steroids do not inhibit sterol synthesis in mouse liver cell or fibroblast cultures under conditions where derivatives of cholesterol oxygenated in the 7, 20, 22 or 25 positions are highly inhibitory. These inhibitory sterols, at concentrations of 0.02–0.2 µg ml−1 specifically depress the activity of the regulatory enzyme in the sterol synthetic pathway, 3-hydroxy-3-methylgrutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), within 6 h.
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