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

[摘要] Purpose: We hypothesize that sexsteroids induce sex-specific and/or opposite effects in the lacrimaland meibomian glands and that these actions may influence theprevalence of dry eye syndrome. The objective of this study was tobegin to test this hypothesis. Methods: Lacrimal and meibomian glandswere obtained from ovariectomized mice that had been treated withtestosterone or control vehicle for 14 days. Samples were processed forthe isolation of RNA, and analyzed for differentially expressed mRNAsusing CodeLink Bioarrays and quantitative real-time PCR (qPCR)techniques. Data were compared to those obtained following testosteronetreatment of orchiectomized mice, as well as after the administrationof 17β-estradiol and/or progesterone to ovariectomized mice. Results: Our findings demonstrate thattestosterone regulates the expression of thousands of genes in thelacrimal and meibomian glands of ovariectomized mice. The magnitude andextent of these hormonal effects, which encompassed numerousbiological, molecular, and cellular ontologies, was tissue-dependent.Particularly notable was the androgen stimulation of meibomian glandgenes related to lipid metabolic pathways, and the suppression of genesassociated with keratinization. Many of the genes regulated bytestosterone in female tissues were identical to those controlled byandrogens in male lacrimal and meibomian glands. However, some geneswere modulated in a sex-specific manner. In addition, a number of theandrogen-regulated genes in female glands were altered in the oppositedirection by 17β-estradiol and/or progesterone. Conclusions: Our results support ourhypothesis that sex steroids may induce sex-specific and/or oppositeeffects in the lacrimal and meibomian glands. Whether these actionscontribute to the prevalence of dry eye remains to be determined.

[学科分类] 生物化学/生物物理