Effects of 17β-Estradiol on Hepatic Fibrosis in Male Rats

Objective To evaluate the relationship between serum testosterone (T) and anti-fibrogenesis of 17β-estradiol (β-Est). Methods Liver fibrosis was induced by CCl4 administration. The fibrosis-suppressive effect of β-Est (20 μg·kg-1·d-1 ) was evaluated in the intact or gonadectomized male rat model. The serum levels of liver enzyme, extracelluar matrix (ECM) and sex hormone were determined by standard enzymatic methods, ELISA and RIA, respectively; the degrees of fibrosis in the liver were determined by VG stain; transforming growth factor-β1 (TGF-β1 ) and activin βA( ACTβA) expressions in the liver were studied by immunohistochemistry and semiquantita-tive RT-PCR. Results All the changes made it clear that β-Est treatment could improve the serum levels of liver enzyme, reduce ECM secretion, suppress hepatic collagen deposition and decrease TGF-β1 and ACTβA expression in the gonadectomized male rat model significantly, but not in the intact male rat model despite attaining the same serum estradiol ( E2 ) levels. Conclusion β-Est could reduce CCl4-induced hepatic fibrosis in rats, but the resistance to the protective effects of estrogen in the male appears to depend on the presence of testosterone. This may be one reason for the sex associated differences in the progression from hepatic fibrosis to cirrhosis.