Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro.
BACKGROUND
Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.


OBJECTIVE
To examine the inhibitory effect of oestradiol on stellate cell activation.


METHODS
In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.


RESULTS
In the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express alpha smooth muscle actin (alpha-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, alpha-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.


CONCLUSIONS
The antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis
Shimizu
I
I
Second Department of Internal Medicine, School of Medicine, University of Tokushima, Tokushima, Japan.
Mizobuchi
Y
Y
Yasuda
M
M
Shiba
M
M
Ma
Y R
YR
Horie
T
T
Liu
F
F
Ito
S
S
D000818:Animals; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D003094:Collagen / Q000096:biosynthesis; D004128:Dimethylnitrosamine; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D004958:Estradiol; D003094:Collagen; D004128:Dimethylnitrosamine