17 beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver

The liver plays important roles in the clearance and metabolism of sex ster oids. Its dysfunction is considered to influence the metabolic pathways of sex steroids, and to result in gynecomastia and other abnormalities of sex steroids. However, the details of its mechanism have not been well-characte rized. We therefore examined the enzymes involved in the hepatic clearance and/or metabolism of sex steroids in human liver and its disorders using im munohistochemistry to determine whether there are any abnormalities of expr ession of these enzymes in human liver disorders. These enzymes are 17 beta -hydroxysteroid dehydrogenase (17 beta -HSD) type 2, an enzyme that cataly zes the biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (E1), and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes sulfonation of dehydroepiandrosterone (DHEA) to form biologicall y inactive DHEA-S. A total of 162 cases including normal Liver (n=31), chro nic hepatitis (n=41), liver cirrhosis (n=21), hepatocellular carcinoma (n=4 7), cholangiocellular carcinoma (n=22) and fetal liver (n=4) were examined by immunohistochemistry. Both enzymes were expressed in the hepatocytes aro und portal area and central vein in normal liver. Immunopositive area for D HEA-ST was significantly larger in chronic hepatitis than in normal liver, but that of 17 beta -HSD type 2 in chronic hepatitis was not different from normal liver. There were no significant differences in the immunopositive area for both enzymes between liver cirrhosis and normal liver. In hepatoce llular carcinoma, immunoreactivity for both enzymes were categorized into G roup A, or low positive group, and Group B, or high positive group. The lat ter tended to be poorly differentiated carcinoma. In cholangiocellular carc inoma, immunopositive areas of both enzymes were significantly smaller than those of normal liver. These findings indicate that the amount of expressi on of the enzymes involved in metabolism and/or clearance of sex steroids p er hepatocyte did not decrease in liver cirrhosis. Therefore, sex steroids' abnormalities may be due to the decreased quantity of hepatocytes associat ed with liver cirrhosis. In hepatocellular carcinoma, some poorly different iated cases were associated with increased expression of 17 beta -HSD type 2 but its biological significance needs to be determined by further studies .