The Effect of X-Irradiation on the Conjugation of Steroids by Mouse Liver and Kidney

Abstract

Radiation has been shown to produce a typical stress response in adrenal glands (1-3). This response is typified by a decrease in adrenal cholesterol (2). It has been demonstrated that an increase in plasma 17-hydroxycorticosteroids occurs shortly after doses of 50 to 800 r of total-body X-irradiation (4). The degree of increase and the duration of elevation were related to dose. Other workers have demonstrated that y-irradiation and internally deposited radionuclides have altered quantitatively adrenal metabolism (5-7). Recently, it has been shown that radiation uncouples oxidative phosphorylation in spleen and liver (8, 9). The uncoupling of oxidative phosphorylation in spleen is mediated via the pituitarythyroid axis, and uncoupling of oxidative phosphorylation in the liver is mediated via the pituitary-adrenal axis (8). Since adrenal steroid production is altered after irradiation, it then becomes important to determine whether or not this alteration in production is associated with changes in the excretory metabolism of these corticosteroids. This is necessary in order to determine if the changes in plasma corticosteroids are a result of altered production, or if they are due to altered elimination from the animal, or both. The major organ of corticosteroid metabolism and excretion is the liver (10). The kidney is also important in the conjugation and excretion of steroids (10, 11). The major route of inactivation and excretion in the liver is the reduction of A4-3-ketone in ring A followed by the conjugation with glucuronic acid at the 3-hydroxyl group to form a water-soluble glucuronide which is excreted in the bile. The liver can also form other conjugates (10). The only source of glu-