Glucuronidation of hydroxy-compounds of testosterone and androstenedione by the microsomal UDP glucuronyl transferase of rat liver

Abstract

The microsomal UDP glucuronyl transferase exhibits activities against hydroxy derivatives of androstenedione (hydroxyl groups in the positions 2β, 6β or 16α) between 5% and 27% of the extent shown against testosterone. 2β-, 6β· and 16α-hydroxyl groups are much less efficient in accepting the glucuronic acid than the 17β-hydroxyl group. However, the acceptor function of the 17β-hydroxyl group is restricted by other hydroxy substituents in the testosterone molecule to an increasing extent represented by the following sequence: 2α, 6β, 6α, 16α, and 7α. A special case is represented by 2β-hydroxy-testosterone. The transferase displays a higher activity against this compound than against testosterone. Apparently the transferase approaches the steroid molecule from the α-side (with the β-side there is also contact at the C-6 atom) requires the 17β-hydroxyl group and the 3-oxo-4-ene system to display full activity. Thus the very high specificity of the transferase for testosterone explains the selective action of this enzyme on testosterone metabolism in the liver. This action is expressed by the fact, that in liver perfusates the percentage of testosterone in the glucuronide fraction is twice as large as the percentage of testosterone in the free steroid fraction.