Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats.
OBJECTIVE
To examine the effects 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.


CONCLUSIONS
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.
Shimizu
I
I
Second Department of Internal Medicine, Tokushima University School of Medicine, Japan.
Yasuda
M
M
Mizobuchi
Y
Y
Ma
Y R
YR
Liu
F
F
Shiba
M
M
Horie
T
T
Ito
S
S
D015073:2-Acetylaminofluorene; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D011944:Receptors, Androgen / Q000032:analysis; D011959:Receptors, Estradiol / Q000032:analysis; D013739:Testosterone / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D011959:Receptors, Estradiol; D004052:Diethylnitrosamine; D013739:Testosterone; D004958:Estradiol; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase