Regulation of Hepatic 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase

Abstract

Abstract Rat hepatic 3-hydroxy-3-methylglutaric acid-coenzyme A reductase (mevalonate:NADP oxidoreductase (acylating CoA) EC 1.1.1.34) exhibits a complex developmental pattern with significant changes occurring prior to birth, after the first postnatal week, and following weaning. The increase in reductase activity that follows weaning cannot be prematurely induced by administration of thyroxine, hydrocortisone, or somatotropin but is invoked by early weaning. Delayed weaning blocks the normal increase, indicating that dietary factors are responsible for the observed changes. The reductase activity in livers from suckling pups exhibits an inverted cyclic rhythm of reduced amplitude, while that of weaned pups has a normal adult type rhythm. The transition from pre- to post-weaned reductase levels appears to involve both the biosynthetic capacity of the diurnal rhythm and relief of inhibition of reductase activity. While suckling rat liver cytosol contains an inhibitor of 3-hydroxy-3-methylglutaric acid-CoA reductase activity, the livers of suckling rats with severed bile ducts exhibit normal adult reductase levels. Rat milk also contains an inhibitor of 3-hydroxy-3-methylglutaric acid-CoA reductase activity.