title: The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice.
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.
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .|2 Department of Nephrology and Endocrinology, Weinan Central Hospital , Weinan, China .
authors.forename: Lianye
authors.initials: L
authors.lastname: Liu
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Liping
authors.initials: L
authors.lastname: Wu
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Aibo
authors.initials: A
authors.lastname: Gao
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lv
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Chuanqing
authors.initials: C
authors.lastname: Xie
authors.affiliation: 3 Department of Epidemiology and Biostatistics, School of Public Heath, Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.affiliation: 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center , Xi'an, China .
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019610:Cytoprotection; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006111:Graves Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000494:pharmacology*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D007376:Interleukin-2; D020011:Protective Agents; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D013196:Dihydrotestosterone; D007371:Interferon-gamma