Lianye Liu1,2, Liping Wu1, Aibo Gao1, Qi Zhang1, Hongjun Lv1, Li Xu1, Chuanqing Xie1, Qian Wu3, Peng Hou1, Bingyin Shi1. 1. 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China . 2. 2 Department of Nephrology and Endocrinology, Weinan Central Hospital , Weinan, China . 3. 3 Department of Epidemiology and Biostatistics, School of Public Heath, Xi'an Jiaotong University Health Science Center , Xi'an, China .
Abstract
BACKGROUND: Graves' disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism that has significant sex differences in prevalence and clinical expressions. Abnormal cytokine production and T cell activation may result in various manifestations of GD. Studies have shown that androgen treatment can provide protection against autoimmune diseases, but the effects of androgen treatment on GD are still unknown. Therefore, this study investigated whether a potent bioactive androgen, 5α-dihydrotestosterone (DHT), could be of benefit in a BALB/c mouse model of GD. The aims of this study were to investigate (i) whether DHT pretreatment inhibits autoimmune responses, and (ii) the mechanism of immune protection of DHT in GD. METHODS: Female BALB/c mice were immunized three times with an adenovirus expressing the human thyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Three doses (1.5, 5, and 15 mg) of DHT or a matching placebo were implanted a week before the first immunization. Four weeks after the third immunization, mice were sacrificed, and blood, the spleen, and the thyroid were removed for further analysis. RESULTS: After DHT treatment, thyroid hormones were dramatically reduced compared with placebo. In addition, a remarkable reduction in interferon-γ and interleukin-2 production was observed in DHT-pretreated mice. CONCLUSIONS: DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.
BACKGROUND:Graves' disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism that has significant sex differences in prevalence and clinical expressions. Abnormal cytokine production and T cell activation may result in various manifestations of GD. Studies have shown that androgen treatment can provide protection against autoimmune diseases, but the effects of androgen treatment on GD are still unknown. Therefore, this study investigated whether a potent bioactive androgen, 5α-dihydrotestosterone (DHT), could be of benefit in a BALB/c mouse model of GD. The aims of this study were to investigate (i) whether DHT pretreatment inhibits autoimmune responses, and (ii) the mechanism of immune protection of DHT in GD. METHODS: Female BALB/c mice were immunized three times with an adenovirus expressing the humanthyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Three doses (1.5, 5, and 15 mg) of DHT or a matching placebo were implanted a week before the first immunization. Four weeks after the third immunization, mice were sacrificed, and blood, the spleen, and the thyroid were removed for further analysis. RESULTS: After DHT treatment, thyroid hormones were dramatically reduced compared with placebo. In addition, a remarkable reduction in interferon-γ and interleukin-2 production was observed in DHT-pretreated mice. CONCLUSIONS:DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.