Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in foetal rats by maternal cholestyramine feeding

Late gestation foetus from rats fed a non-absorbable bile acid binding resin (cholestyramine) have increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. This was due to increased unphosphorylated (active) as well as total reductase and was accompanied by higher fatty acid synthetase activity. No increase in foetal hepatic cystathionase or tyrosine aminotransferase activity, or changes in plasma insulin, corticosterone or thyroxine were found. The studies demonstrate that foetal hepatic cholesterol metabolism is sensitive to drug-induced perturbation of maternal lipoprotein metabolism. The data suggest induction of foetal cholesterol and fatty acid synthesis by a specific mechanism not involving generalized hormone-induction of hepatic enzyme systems. Cholestyramine appears to have application for in vivo study of the regulation of foetal cholesterologenesis and its coordination to maternal and foetal steroid requirements.