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F. Schirra, S.M. Richards, D.A. Sullivan; Androgen Control of lipogenic Gene Expression in the Mouse Meibomian Gland. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3871.
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Purpose. We have found that androgens increase the expression of genes encoding lipogenic enzymes (e.g. sterol regulatory element binding proteins 1 and 2, fatty acid synthase, ATP–citrate lyase, acetyl–CoA–carboxylase) in the mouse meibomian gland. Given these results, we hypothesize that androgens stimulate lipogenesis in this tissue. To begin to test this hypothesis, we examined whether androgens enhance the mRNA levels of enzymes involved in cholesterol synthesis. Methods. Meibomian glands were obtained from orchiectomized mice (n = 6–22/treatment group; n = 4 experiments), that were treated with vehicle or testosterone for 2 weeks. Tissues were processed for the isolation of DNA–free RNA and the analysis of selected mRNAs by real–time PCR. Gene expression was standardized to the levels of glyceraldehyde–3–phosphate dehydrogenase mRNA and calculations were based on the standard curve method of relative quantitation of gene expression. Results. Our results demonstrate that androgens upregulate the mRNA levels of most of the key, cholesterol pathway enzymes in the meibomian gland. These enzymes include 3–hydroxy–3–methylglutaryl coenzyme A (HMG–CoA) reductase, mevalonate kinase, phospho mevalonate kinase (2 studies), mevalonate pyrophosphate decarboxylase, isopentenyl pyrophosphate isomerase, geranylgeranyl pyrophosphate synthase, squalene epoxidase, lanosterol demethylase and Δ7–sterol reductase, and possibly HMG–CoA synthase. In contrast, androgen exposure downregulated the gene expression for lathosterol oxidase. Conclusions. These findings support our hypothesis that androgens stimulate lipogenesis in the meibomian gland. (Supported by research grants from NIH [EY05612], Allergan and the German Research Society DFG)
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