Estrogens interact in a variety of ways with the liver. Not only is the liver an estrogen-responsive tissue, but it is also responsible for the interconversion, metabolism and excretion of the estrogens. The effect of liver disease on these processes has not been studied well, except in the specific case of alcohol-induced liver disease. Therefore, using five well-characterized animal models of liver diseases, we will assess the effect of a variety of liver diseases on several aspects of estrogen metabolism in the male rat. First, the potential responsiveness of the liver to estrogens will be evaluated by quantitation of cytosolic receptors in both the diseased and normal livers as well as by determination of the affinity of the receptors for estrogen. Second, we will assess changes in the levels and/or affinity of male-specific estrogen binding protein whose proposed role is that of an estrogen scavenger. Third, the synthesis and tissue levels of the catechol estrogens (2-hydroxy estrogens) will be examined in rats with diseased and normal livers. These compounds are of interest because they are major metabolites of the estrogens in the liver, and, additionally, because they have been shown to interfere with P-450-related drug metabolism in the liver. Therefore, since alterations in any one of these various aspects of hepatic estrogen metabolism could adversely effect individuals with liver disease, an evaluation of various types of liver disease on these individual processes should be meaningful. Moreover, this study should provide a basis for the understanding of the effect of specific types of liver disease upon various aspects of estrogen metabolism and thus the effect of such alterations upon the individual.