Conjugation and biliary excretion of corticosteroids by isolated perfused liver

Abstract

The metabolic capacities of the liver on cortisol and corticosterone were studied using the isolated perfused rat liver with cannulated biliary duct, a preparation in which temperature, blood pressure, and injection mass can be rigidly maintained. The infused steroids were 4-C¹⁴-labeled compounds in trace amount (3–5 µg). The major transformation achieved by the liver is conjugation of the steroids, which renders them water soluble and rapidly excretable in the bile. The half-lives (T1/2) of the steroids we found in blood are shorter than those reported for intact animals; however, differences in the T1/2 of the metabolic products of both steroids (cortisol > corticosterone), speed of excretion (cortisol < corticosterone), and rate of conjugation (cortisol < corticosterone) were found to be in agreement with those found in the in vivo studies. Whereas, in normal humans, most of the steroids are excreted in the urine as ß-glucuronides and sulfates, these types of conjugates accounted for less than 30% of the water-soluble compounds recovered from the bile in the present study. Finally, none of the originally injected steroid was found to be present in the bile.