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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:600333 |
| Date | January 2014 |
| Creators | Ali, Farrah Z. |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/4934/ |
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