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H. C. Woll, B. Seitz, Z. Gatzioufas, F. Schirra; Androgens Regulate the Peroxisome Proliferator-Activated Receptor Signaling Pathway in the Mouse Meibomian Gland. Invest. Ophthalmol. Vis. Sci. 2008;49(13):95.
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© ARVO (1962-2015); The Authors (2016-present)
To demonstrate the relevance of androgen influence on the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the mouse meibomian gland. This tissue is the primary source of the tear film lipid layer and indispensable for ocular surface health.
Orchiectomized mice were systemically treated with either testosterone or placebo for two weeks. The mRNA was then extracted from the meibomian glands and differential gene expression was investigated by microarray hybridisation and evaluation with GeneSifter software as well as pathway information of the Kyoto Encyclopedia of Genes and Genomes (KEGG).
The PPAR signaling pathway was identified as one of the most extensively testosterone-influenced pathways in the mouse meibomian gland. Specifically, 3-hydroxy-3-methylglutaryl-Coenzyme A (CoA) synthase 2, Acyl-CoA dehydrogenase long chain, and Fatty acid desaturase 2 were significantly down-regulated, whereas Acyl-CoA synthetase long chain family members 4 + 5, Acyl-CoA dehydrogenase medium chain, Acyl-CoA oxidases 1 + 3, Apolipoprotein A-V, Fatty acid binding protein 3, Malic enzyme, PPAR delta, Retinoid X receptor gamma, Stearoyl-CoA desaturases 1, 2 + 3, and Sterol carrier protein 2 were significantly up-regulated. Regulated genes of the PPAR signaling pathway are involved in ketogenesis, lipid transport, lipogenesis, fatty acid transport, and fatty acid oxidation.
The profound regulation of the lipid-associated PPAR signaling pathway by testosterone may clarify the impact of this sex steroid on the meibomian gland and explain, at least in part, its protective functions in ocular surface health.
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