title: Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway.
abstract: Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway.
authors: Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
authors: Guangda
authors: G
authors: Xin
authors: Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
authors: Shaoyou
authors: S
authors: Qin
authors: Department of Urology, The Second Hospital of Jilin University, Changchun 130041, PR China.
authors: Song
authors: S
authors: Wang
authors: Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
authors: Xu
authors: X
authors: Wang
authors: Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
authors: Yonggui
authors: Y
authors: Zhang
authors: Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China zrlwangjb@medmail.com.cn.
authors: Jiangbin
authors: J
authors: Wang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D013739:Testosterone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Non-alcoholic steatohepatitis; TLR-MyD88-IL-6 signaling pathway; sex hormone-specific intervention; sex-associated differences