Role of testosterone in regulating induction of TNF-α in rat spleen via ERK signaling pathway

被引：19

作者：

Chen, Chien-Wei ^{[1
]}

Jian, Cai-Yun ^{[1
]}

Lin, Po-Han ^{[1
]}

Chen, Chih-Chieh ^{[1
]}

Lieu, Fu-Kong ^{[2
]}

Soong, Christina ^{[2
]}

Hsieh, Chu-Chun ^{[1
]}

Wan, Chi-Yun ^{[1
]}

Idova, Galina ^{[9
]}

Hu, Sindy ^{[7
,8
]}

Wang, Shyi-Wu ^{[3
,7
]}

Wang, Paulus S. ^{[1
,4
,5
,6
]}

机构：

[1] Natl Yang Ming Univ, Sch Med, Dept Physiol, Taipei 11221, Taiwan

[2] Cheng Hsin Gen Hosp, Dept Rehabil, Taipei 11280, Taiwan

[3] Chang Gung Univ, Dept Physiol & Pharmacol, Coll Med, Taoyuan 33302, Taiwan

[4] China Med Univ Hosp, Med Ctr Aging Res, Taichung 40402, Taiwan

[5] Asia Univ, Dept Biotechnol, Coll Hlth Sci, Taichung 41354, Taiwan

[6] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei 11217, Taiwan

[7] Chang Gung Mem Hosp, Dept Dermatol, Aesthet Med Ctr, Taoyuan 33305, Taiwan

[8] Chang Gung Univ, Dept Med, Coll Med, Taoyuan 33302, Taiwan

[9] State Sci Res Inst Physiol & Basic Med, Timakova St 4, Novosibirsk 630117, Russia

来源：

STEROIDS | 2016年 / 111卷

关键词：

Testosterone; Orchidectomy; Splenocyte; Inflammation; TNF-alpha; RECEPTOR; SPERMATOGENESIS; STEROIDOGENESIS; INFLAMMATION; SECRETION; RESPONSES; FAMILY; MEN;

D O I：

10.1016/j.steroids.2016.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (2 mg/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-alpha) 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-alpha and NO secretion in response to LPS were confirmed in the rat splenocytes. Testosterone also significantly attenuated LPS-elicited release of TNF-alpha 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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：148 / 154

页数：7

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