Taurocholate inhibits the glucocorticoid-induced rise of 3-hydroxy-3-methylglutaryl-CoA reductase in primary culture of hepatocytes.

The influence of taurocholate, the major bile acid of the rat, on 3-hydroxy-3-methylglutaryl-CoA reductase [mevalonate: NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34], the regulatory enzyme of cholesterol synthesis, was studied in primary cultures of rat hepatocytes. The basal activity of the enzyme was not altered by adding up to 10 microM taurocholate to the culture medium. On the contrary, 1nM to 10 microM taurocholate caused a dose-dependent inhibition of enzyme activity within 6 h if added simultaneously with 10 microM dexamethasone. Because this glucocorticoid causes a cycloheximide-sensitive rise of 3-hydroxy-3-methylglutaryl-CoA reductase activity in this system the results are taken as evidence that bile salts inhibit the synthesis of the enzyme. The induction of tyrosine transaminase (L-tyrosine:2-oxoglutarate aminotransferase; EC 2.6.1.5) by dexamethasone was not influenced by taurocholate, which demonstrates that the glucocorticoid sensitivity of the cells was not impaired by the bile salt. It is concluded that there is a direct control of hepatic cholesterol synthesis by bile salts.