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M Liu, SM Richards, F Schirra, DA Sullivan; Sex and Androgen Influence on Gene Expression in Lacrimal Glands of Normal and Autoimmune Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3145.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Sjögren's syndrome (SS) is an autoimmune disorder that occurs almost exclusively in women and is associated with lacrimal gland inflammation and severe dry eye. The progression of this disease has been linked to androgen deficiency, given that women with SS are androgen-deficient and that androgen administration to female mouse models of SS suppresses the inflammation in, and improves the function of, lacrimal glands. The purpose of this study was to determine whether specific genes may contribute to the gender-related prevalence, as well as the androgen suppression, of lacrimal gland inflammation in SS. Methods: Lacrimal glands were obtained from adult BALB/c, Tfm (androgen receptor mutant), Tabby (Tfm control) and autoimmune MRL/lpr and NOD mice (n = 10 to ≷20/group). Mice were either intact or orchiectomized and treated with placebo or testosterone for 2 weeks. Tissues were processed for the analysis of differentially expressed mRNAs by using Incyte GEM 1 (≷ 8,000 genes) and GEM 2 (≷ 9,500 genes) gene chips and Rosetta Resolver software. The expression of selected genes was confirmed by real-time PCR. Results: Our results show that gender (BALB/c = 765 genes; MRL/lpr = 108; NOD = 214), testosterone treatment (BALB/c = 147; MRL/lpr = 140) and androgen receptor mutation (Tfm = 91) significantly influence the expression of many genes in lacrimal tissues of non-autoimmune and autoimmune mice. These genes are involved in a wide array of functions, such as lipid and sugar metabolism, transport, trafficking, signal transduction, transcription, steroidogenesis, protease activity, cytokine/chemokine networks, cell adhesion and apoptosis. Of interest, gene chips indicated that arginine vasopressin (i.e. antidiuretic hormone, which is pro-inflammatory and decreases fluid secretion) mRNA was upregulated in inflamed lacrimal tissues of MRL/lpr and NOD mice, and apparently downregulated by androgen treatment in MRL/lpr lacrimal glands. Conclusion: Numerous genes appear to contribute to the gender-related prevalence and androgen suppression of lacrimal gland inflammation in SS. Supported by NIH grants EY05612 and EY12523, Allergan and the German Research Society DFG.
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