title: Role of testosterone in regulating induction of TNF-α in rat spleen via ERK signaling pathway.
abstract: Spleen is a pivotal organ for regulating immune homeostasis. It has been shown that testosterone diminishes secretion of various inflammatory molecules under multiple conditions. However, the mechanisms of action of endogenous testosterone affecting immune responses in the spleen remain unknown. The aim of the present study was to evaluate the immune functions of the spleen in response to testosterone withdrawal after orchidectomy, and the impact of splenocytes on the bacterial endotoxin lipopolysaccharide (LPS)-induced secretion of inflammatory molecules. Male rats were divided into 3 groups, i.e. intact, orchidectomized (Orch) and orchidectomized plus replacement of testosterone propionate (TP) (Orch+TP). The Orch and Orch+TP rats underwent bilateral orchidectomy one week before TP replacement (2mg/kg body weight) or sesame oil in intact rats as controls for seven days. Orch resulted in a significant increase of spleen weight and basal secretion of nitric oxide (NO) from splenocytes. Additionally, LPS up-regulated cell proliferation and the secretion of tumor necrosis factor-alpha (TNF-α) in splenocytes of Orch rats. Orch further up-regulated phosphorylation of extracellular signal-regulated kinases. Interestingly, the plasma corticosterone concentration in the Orch group was higher than that in the intact and Orch+TP groups. Deficiency of testosterone-elevated TNF-α and NO secretion in response to LPS were confirmed in the rat splenocytes. Testosterone also significantly attenuated LPS-elicited release of TNF-α and NO in a dose-dependent manner. However, testosterone did not suppress splenic blastogenesis at doses in the 10(-10)-10(-7)M concentration range. In this context, testosterone might have a protective role against inflammatory responses in the spleen. The present study provides evidence to indicate that testosterone might modulate the immune system.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Jian
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Lin
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Rehabilitation, Cheng Hsin General Hospital, Taipei 11280, Taiwan.
authors.forename: Fu-Kong
authors.initials: FK
authors.lastname: Lieu
authors.affiliation: Department of Rehabilitation, Cheng Hsin General Hospital, Taipei 11280, Taiwan.
authors.forename: Christina
authors.initials: C
authors.lastname: Soong
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chu-Chun
authors.initials: CC
authors.lastname: Hsieh
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chi-Yun
authors.initials: CY
authors.lastname: Wan
authors.affiliation: State Scientific Research Institute of Physiology and Basic Medicine, Timakova Street, 4, Novosibirsk 630117, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Idova
authors.affiliation: Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Sindy
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan. Electronic address: swwang@mail.cgu.edu.tw.
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; Medical Center of Aging Research, China Medical University Hospital, Taichung 40402, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung 41354, Taiwan; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan. Electronic address: pswang@ym.edu.tw.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Inflammation; Orchidectomy; Splenocyte; TNF-α; Testosterone