17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver.
The liver plays important roles in the clearance and metabolism of sex steroids. 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-characterized. We therefore examined the enzymes involved in the hepatic clearance and/or metabolism of sex steroids in human liver and its disorders using immunohistochemistry to determine whether there are any abnormalities of expression of these enzymes in human liver disorders. These enzymes are 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2, an enzyme that catalyzes the biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (El), and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes sulfonation of dehydroepiandrosterone (DHEA) to form biologically inactive DHEA-S. A total of 162 cases including normal liver (n=31), chronic hepatitis (n=41), liver cirrhosis (n = 21), hepatocellular carcinoma (n = 47), cholangiocellular carcinoma (n = 22) and fetal liver (n = 4) were examined by immunohistochemistry. Both enzymes were expressed in the hepatocytes around portal area and central vein in normal liver. Immunopositive area for DHEA-ST was significantly larger in chronic hepatitis than in normal liver, but that of 17beta-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 hepatocellular carcinoma, immunoreactivity for both enzymes were categorized into Group A, or low positive group, and Group B, or high positive group. The latter tended to be poorly differentiated carcinoma. In cholangiocellular carcinoma, immunopositive areas of both enzymes were significantly smaller than those of normal liver. These findings indicate that the amount of expression of the enzymes involved in metabolism and/or clearance of sex steroids per hepatocyte did not decrease in liver cirrhosis. Therefore, sex steroids' abnormalities may be due to the decreased quantity of hepatocytes associated with liver cirrhosis. In hepatocellular carcinoma, some poorly differentiated cases were associated with increased expression of 17beta-HSD type 2 but its biological significance needs to be determined by further studies.
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
T
T
Narasaka
T
T
Moriya
M
M
Endoh
T
T
Suzuki
S
S
Shizawa
Y
Y
Mizokami
T
T
Matsuoka
H
H
Sasano
D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis* / Q000378:metabolism; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D018281:Cholangiocarcinoma / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005260:Female; D006521:Hepatitis, Chronic / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015238:Sulfotransferases / Q000032:analysis* / Q000378:metabolism
D004967:Estrogens; D007527:Isoenzymes; D004970:Estrone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D015067:17-Hydroxysteroid Dehydrogenases; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase