Gender differences in T cell regulation and responses to sex hormones

Ali, Farrah Z. (2014). Gender differences in T cell regulation and responses to sex hormones. University of Birmingham. Ph.D.

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Abstract

Conflicting effects of sex hormones could potentially explain the increased susceptibility of females developing autoimmune diseases. In this study I found that 5\(\alpha\)-reductase expression both on the mRNA and protein was unregulated in female T cells after stimulation, which was not observed in the male T cells. This was particularly interesting as 5\(\alpha\)-reductase is responsible for the synthesis of the most potent androgen DHT, which has shown to exert anti-inflammatory effects. I did not observe any significant differences in 5\(\alpha\)-reductase expression in T cells between SLE patients and healthy controls. However, I did find a significantly higher expression of 5\(\alpha\)-reductase in B cells from SLE patients compared to healthy controls. In vitro treatment of testosterone showed that high concentrations the proportion of IL-2-producing female CD4 T cells decreased (not in the male T cells) and lower concentrations had the opposite effect. This latter observation was shown to be oestrogen-dependent as experiments using tamoxifen abolosihed the effect. Overall, sex differences are present in the expression of 5\(\alpha\)-reductase in T cells upon stimulation and regulation of 5\(\alpha\)-reductase expression is altered in SLE B cells. IL-2 production is sensitive to changes in testosterone concentration and there is an element of gender dimorphism in the T cell response to testosterone.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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