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N. Martin, Z. Gatzioufas, B. Seitz, F. Schirra; Testosterone Regulates the Pyruvate Metabolism Pathway in the Mouse Meibomian Gland. Invest. Ophthalmol. Vis. Sci. 2008;49(13):94.
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To demonstrate the relevance of androgen influence on the pyruvate metabolism in the mouse meibomian gland. Pyruvate metabolism is central to lipid metabolism. The meibomian gland is the primary source of the tear film lipid layer and crucial for a healthy ocular surface.
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 pyruvate metabolism pathway was the most comprehensively testosterone-influenced pathway in the mouse meibomian gland. More specifically, Acyl-CoA synthetase short-chain family member 2, Acyl-CoA thioesterase 12, Acylphosphatase 2 muscle type, Aldehyde dehydrogenase 9 subfamily A1, Hydroxyacylglutathione hydrolase-like, Malate dehydrogenase 1 NAD (soluble), Malate dehydrogenase 2 NAD (mitochondrial), Malic enzyme supernatant, Pyruvate dehydrogenase E1 alpha 1 and -alpha 2, Pyruvate kinase liver and red blood cell, Pyruvate kinase muscle were significantly up-regulated. Only Aldehyde dehydrogenase family 3 subfamily A2 was significantly down-regulated.
The comprehensive activation of the pyruvate metabolism pathway in the meibomian gland by testosterone works towards supply of substrate for lipid synthesis. This explains, at least in part, the beneficial impact of androgens on meibomian gland function, and thus, on ocular surface health.
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