Regulation of perfluorooctanoic acid–induced peroxisomal enzyme activities and hepatocellular growth by adrenal hormones

Abstract

A wide variety of compounds, including hypolipidemic drugs, plasticizers and other industrial chemicals, have been found to cause liver enlargement and hepatic peroxisome proliferation by mechanisms that are unclear. Although thyroid and sex hormones have been shown to modulate the hepatic response to these chemicals, the role of adrenal hormones in these phenomena is not clear, and a few studies have produced conflicting data. Therefore this study was undertaken to investigate the role of adrenal hormones in hepatomegaly and peroxisomal enzyme induction caused by peroxisomal proliferators and to further delineate the interrelationship between these parameters. Because adrenalectomy alters hepatic drug metabolism, we have used the nonmetabolizable proliferator perfluorooctanoic acid. Our data show that hepatomegaly caused by perfluorooctanoic acid depends on corticosterone, the major glucocorticoid in rodents. Liver growth caused by perfluorooctanoic acid appears to be predominantly hypertrophic in nature, and DNA synthesis in response to perfluorooctanoic acid predominates in periportal regions of the liver lobule. Data also show that although induction of peroxisomal beta-oxidation by perfluorooctanoic acid is independent of adrenal hormones, induction of catalase is dependent on the presence of these hormones. This study supports the contention that induction of activities of various peroxisomal enzymes is controlled by different regulatory mechanisms.