Akio Ito

Androgen receptors in hepatocellular carcinoma and surrounding parenchyma

The androgen receptor content of normal human liver, hepatocellular carcinoma, and surrounding liver tissue was determined in patients with chronic liver disease. Androgen receptor was detected in all six normal livers obtained from 4 men and 2 women. The androgen receptor content in these 6 individuals ranged from 5.0 to 10.2 fmol/mg protein (Kd 10.6-31.8 X 10(-10) M). The livers from 2 patients with chronic active hepatitis and from 10 cirrhotic patients with hepatocellular carcinoma had detectable amounts of androgen receptor ranging from 2.0 to 14.8 fmol/mg protein (Kd 4.0-30.9 X 10(-10) M). Androgen receptor was found in the cytosol of 14 of 19 men with hepatocellular carcinoma. The titer ranged from 3.7 to 45.4 fmol/mg protein (Kd 3.2-21.4 X 10(-10) M). Hepatocellular carcinoma had a significantly higher concentration of androgen receptor than did the surrounding cirrhotic liver tissue. In 2 men and 1 woman, androgen receptor was detected in the cirrhotic liver but not in the tumor. In the remaining 3 men, both tumor and cirrhotic liver were negative for androgen receptor.

Estrogen receptors in hepatocellular carcinoma

Estrogen receptors (ER) were assayed on hepatocellular carcinoma (HCC) and surrounding liver tissue in 30 adult patients. All specimens were obtained at the time of surgery. Cirrhosis of the liver was associated with 28 patients and chronic hepatitis in 2 patients. ERs were detected in 12 of 30 HCCs. The value ranged from 1.4 to 9.2 fmol/mg cytosol protein with the dissociation constant (Kd) value less than 1 nanomol. On the other hand, 13 of 28 cirrhotic livers had measurable amounts of the receptors that ranged from 1.5 to 4.1 fmol/mg cytosol protein. Two livers with chronic hepatitis did not have detectable amounts of ERs. The receptors were not detected in both the tumor and liver in ten patients. The ER titers in HCC did not have any correlation with serum levels of α‐fetoprotein or carcinoembryonic antigen, hepatitis B virus profils, and histologic types of the tumor. In the light of the current results, it would be of great interest whether hormone therapy can be used or not as a treatment of naturally occurring HCC in humans.

Serum Levels of Estrogens and Testosterone in Cirrhotic Men With and Without Hepatocellular Carcinoma

Serum levels of estrogens and testosterone were measured in 25 male patients with hepatocellular carcinoma and associated cirrhosis of the liver and in another 25 male patients with cirrhosis only. The two groups were statistically comparable in terms of age distribution, duration of liver disease, incidence of alcohol abuse, incidence of hepatitis B surface antigenemia, and grade of hepatic dysfunction. Estrone was significantly elevated in both groups of patients. Estradiol concentrations were above normal in 10 patients with hepatocellular carcinoma and in 11 with cirrhosis only. All patients had normal concentrations of estriol. There were no statistical differences between the two groups in either individual or total estrogen levels (estrone 0.05 less than p less than 0.1). Eight of the patients with hepatocellular carcinoma and 5 of the cirrhotics had lower testosterone levels than normal, but this difference was not significant. However, the estrone to testosterone ratios were significantly higher in the hepatocellular carcinoma group than in the cirrhosis group (p less than 0.05). The present study seems to indicate that hyperestrogenemia commonly seen in male patients with liver cirrhosis may play some role in hepatic carcinogenesis of cirrhotic livers. Further studies are needed to determine if the estrone to testosterone ratio is implicated in hepatocarcinogenesis in cirrhotic men.

Active uptake of testosterone by androgen receptors of hepatocellular carcinoma in humans

Hepatocellular carcinoma (HCC) is more prevalent in males than it is in females, which has often been explained by the fact that alcoholism and chronic hepatitis B virus infection are more prevalent among males. The current studies, using biochemical and autoradiographic methods, verified that HCC contains higher concentrations of androgen receptors than the surrounding liver parenchyma and that extrinsically given testosterones are actively taken up by such tumors. These results may suggest that HCC is an androgen‐dependent tumor and that, therefore, this tumor is more prevalent in males than it is in females.