Endocrine Abstracts

Objective: Graves’ disease (GD) exhibits a higher prevalence in females compared to males. Sex hormones might influence susceptibility of this disease. Studies have shown that 5α-dihydrotestosterone (DHT) treatment can provide protection against GD. In order to further confirm the protective effect of different forms of androgen against GD and its preventive mechanism, the current investigation was designed to explore gender difference and response to testosterone or DHT treatment in the mice model of GD.

Methods: Female and male BALB/c mice were injected three times at three weekly intervals with adenovirus expressing the human thyrotropin receptor A-subunit to induce GD model. Castration and androgen treatment in mice were conducted a week before the first immunization. Four weeks after the third immunization, the incidence and the severity of GD were observed by the determination of serum TBI, TT4, FT4 of castrated males as well as androgen treated females, and the immune response of Th1/Th2/Th17/Treg were analyzed by measuring the expression and secretion levels of T lymphocyte cytokine from spleen using flowcytometry and ELISA.

Results: Lowered TT4, slightly lowered levels of FT4 and the low proportion of hyperthyroidism were displayed in males compared to females. Both T and DHT significantly reduced the levels of TT4, FT4 and the degree of thyroid hyperplasia. The analysis of T cell flowcytometry showed that the expression of CD4+INF-γ+ among CD4+ T cell in males was lower when compared to females, and androgen depletion mildly increased the percentage of CD4+CD25+ and CD4+CD25+Foxp3+ in CD4+ T cell. Androgen treatment not only significantly inhibited the expression of CD4+INF-γ+, but also promoted the expansion of CD4+CD25+ and CD4+CD25+Foxp3 population within CD4+ T cells. In this study, the ELISA analysis results of cytokine secretion products of T cells also displayed that exogenous androgen treatment inhibited the secretion of INF-γ and IL-10.

Conclusions: Supplemental exogenous androgen treatment provided protection against Graves’ hyperthyroidism in BALB/c genetic background mice. Suppressed Th1 and/or Th2 immune response and extended Tregs population may be one mechanism that is responsible for the protective role of androgen.