Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver.

Abstract

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.