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Background: Extensive keratinization appears to play a major role in the dysfunction of the Meibomian gland. This article presents the potential impact of androgens on limiting keratinization in this tissue, thus, contributing to normal Meibomian gland function and a healthy ocular surface., Materials and Methods: Orchidectomized mice were systemically treated with either testosterone or placebo for 2 weeks. The mRNA was then extracted from the Meibomian glands and differential gene expression was investigated by microarray hybridization and evaluation with GeneSifter software as well as gene ontology information from the Gene Ontology (GO) Consortium., Results: By z-score calculations, keratinization was the most significantly gene ontology term influenced by testosterone based on down-regulated genes in the mouse Meibomian gland. In particular, under the influence of testosterone the genes coding for small proline-rich protein (Sprr) 2a, Sprr 2b, Sprr 3, keratins 6a and 17 and periplakin were significantly down-regulated, while Sprr 1a and Sprr 2f were significantly up-regulated., Conclusions: Testosterone down-regulates the expression of genes promoting keratinization in the Meibomian gland. This may help to prevent Meibomian gland dysfunction by limiting excessive keratinization of this tissue and the adjacent lid margins. The findings elucidate, at least in part, the beneficial impact of androgens on Meibomian gland function and thus on th e health of the ocular surface.

So far, two angiotensin receptor subtypes, called AT1 and AT2, have been described in an animal model and in human. AT1 mediates almost all known effects of angiotensin II and its gene sequence and regulation is well studied. In contrast, only few data on function and regulation of AT2 are available. The complete mRNA sequence of AT2 has only recently been cloned and sequenced. The angiotensin receptors' receptor density and subtype distribution is organ specific. In the rat, lowest densities are found in the myocardium, followed by kidney, liver, adrenal medulla and cortex. The percentage of AT1 in the different organs amounts to 80, 85, 90, 57 and 10%. Angiotensin receptor subtypes have also been quantitated in human myocardium. There, the relatively unknown subtype AT2 dominates (67%). Myocardial receptor density is low, amounting to about 11 fmol/mg protein corresponding to 1/20-1/50 of the density of beta-adrenergic receptors. Angiotensin receptors in the human heart are present on cardiac fibroblasts and induce proliferation of these cells. Blockade of the renin angiotensin system by ACEI and AT1 antagonists in the rat downregulates angiotensin receptors in liver, kidney and adrenals to about 50% in an organ- and subtype specific manner, whereas cyclosporin A upregulates receptors twice. In end-stage human heart failure, but not in early stages, angiotensin receptors are downregulated to 1/3 of control values. Regulator mechanisms at transcriptional level have been elucidated by reporter gene assays; PMA, an activator of proteinkinase C, stimulates the transcription of the AT1 gene. The organ- and subtypespecific regulation of angiotensin receptors by pharmacological agents and/or cardiovascular diseases can contribute to the understanding of these drugs and of the pathophysiology of the corresponding diseases.