Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague-Dawley rats.
OBJECTIVE
We studied the mechanisms of estrogen/androgen involvement in the induction of NASH by treating Sprague-Dawley (SD) rats fed with a normal or high fat (HF) diet by depriving them of endogenous estrogens/androgens.


METHODS
Male adult SD rats (n = 10/group) on normal or HF diets were treated for 75 days either with tamoxifen (Tam) or flutamide (Flu) or Tam + Flu in order to induce NASH. We analyzed histopathologically the liver samples from the treated groups for NASH, checked the serum biochemical and lipid profile markers and finally analyzed the signal pathways underlying the molecular mechanisms for the induction process of NASH.


RESULTS
Deprivation of endogenous estrogens and/or androgens (Tam or Flu or Tam + Flu) without the HF diet did not induce NASH. Tam or Tam + Flu induced NASH, compared to milder lesions without fibrosis in HF diet and Flu-treated liver. Serum alanine aminotransferase or lipid profile markers further proved the Tam, Flu or Tam + Flu effects on the induction of NASH in conjunction with a HF diet. Tam treatment predominantly downregulated the ERalpha and FAS and upregulated UCP2 and TNF-alpha.


CONCLUSIONS
Deprivation of endogenous estrogen/androgens in conjunction with a HF diet may induce NASH where the downregulated ERalpha and FAS, and upregulated UCP2 and TNF-alpha could be involved in their molecular pathomechanism pathways. These results could suggest the potential negative roles of estrogenic/androgenic depriving compounds in the induction of NASH, along with obesity.
Mu
Yanjun
Y
State Key Laboratory of Agro-Biotechnology, Faculty of Biological Sciences, China Agricultural University, Beijing, China.
She
Ruiping
R
Zhang
Hua
H
Dong
Bing
B
Huang
Chengfei
C
Lin
Wei
W
Li
Defa
D
Li
Xiangdong
X