Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?

Purpose: We hypothesize that sex steroids induce sex-specific and/or opposite effects in the lacrimal and meibomian glands and that these actions may influence the prevalence of dry eye syndrome. The objective of this study was to begin to test this hypothesis. Methods: Lacrimal and meibomian glands were obtained from ovariectomized mice that had been treated with testosterone or control vehicle for 14 days. Samples were processed for the isolation of RNA, and analyzed for differentially expressed mRNAs using CodeLink Bioarrays and quantitative real-time PCR (qPCR) techniques. Data were compared to those obtained following testosterone treatment of orchiectomized mice, as well as after the administration of 17βestradiol and/or progesterone to ovariectomized mice. Results: Our findings demonstrate that testosterone regulates the expression of thousands of genes in the lacrimal and meibomian glands of ovariectomized mice. The magnitude and extent of these hormonal effects, which encompassed numerous biological, molecular, and cellular ontologies, was tissue-dependent. Particularly notable was the androgen stimulation of meibomian gland genes related to lipid metabolic pathways, and the suppression of genes associated with keratinization. Many of the genes regulated by testosterone in female tissues were identical to those controlled by androgens in male lacrimal and meibomian glands. However, some genes were modulated in a sex-specific manner. In addition, a number of the androgen-regulated genes in female glands were altered in the opposite direction by 17β-estradiol and/or progesterone. Conclusions: Our results support our hypothesis that sex steroids may induce sex-specific and/or opposite effects in the lacrimal and meibomian glands. Whether these actions contribute to the prevalence of dry eye remains to be determined.