Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats

Abstract

Aims-To examine the eVects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis. Methods-Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay. Results-Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level. Conclusion-These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.

Estrogen Suppresses Metastasis in Rat Hepatocellular Carcinoma through Decreasing Interleukin-6 and Hepatocyte Growth Factor Expression

“…Although many controversies still exist with respect to the association between estrogen and HCC, evidence has been accumulating to show that estrogen may play a protective role against the HCC development in recent years [2,3]. However, currently, it remains unknown whether and how estrogen is linked to the distant metastases of HCC and, if so, which kind of mechanism is involved.…”

“…Recently, accumulating evidence has shown that estrogen has certain protective role against the development of HCC. [2,3] However, data are still scarce about whether and how estrogen affects the distant metastasis of HCC.…”

Gender Disparity of Hepatocellular Carcinoma: The Roles of Sex Hormones

“…In rodent HCC models, ovariectomy was reported able to increase the susceptibility of HCC in female mice [45,46]. Shimizu et al [55] also demonstrated a suppressive effect of estradiol administration in hepatocarcinogenesis using the DEN, 2-acetylaminofluorene, partial hepatectomy HCC model. In contrast, the synthetic estrogen was found to have the ability to promote hepatocarcinogenesis after initiation with DEN treatment [56,57,58], which in turn will not occur in the absence of the initiation event.…”

Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells

“…In addition, HCV-related cirrhotic women before menopause might also have the ability to protect against developing HCC via hepatic ER . Our previous reports also concluded that E2 suppresses hepatic chemical carcinogenesis (Shimizu et al, 1998) in animal models. These findings suggest that the putative cytoprotective and anticarcinogenic roles of E2 in the liver may contribute to the sexassociated differences observed in the development of chronic viral hepatitis.…”