In Vitro Metabolism of Hydrocortisone in Tissues of the Adult Rat

Abstract

Various tissues of the rat were tested for ability to metabolize hydrocortisone from a Krebs-Ringer solution. Whole slices, homogenates and subcellular fractions were tested separately and under various conditions. The liver is capable of handling large amounts of steroid and of degrading both the A-ring and the sidechain. Other tissues are capable of metabolizing smaller quantities of hydrocortisone. Pretreatment of the animal influences the rate of metabolism of steroid by the liver. Administration of cortisone, or thyroxine, increases the ability of the liver to metabolize steroid; hypophysectomy or thyroidectomy reduces the rate of metabolism. The proper use of inhibitors permits the metabolism of either the sidechain or the A-ring selectively. A-ring metabolism is inhibited by DPN, PCMBA, dehydroascorbic acid and DPNH; it is accelerated by TPNH. Metabolism of the sidechain is accelerated by DPN, nicotinamide and TPNH. Metabolism of steroids occurs readily in the microsome fraction of liver and in the acidophilic granules of the pituitary. In the pituitary the fraction containing ACTH was also the fraction metabolizing most of the steroid sidechain.