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D. Talbot, T. Suzuki, S. M. Richards, D. A. Sullivan; Impact of Complete Estrogen Absence on Gene Expression in the Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1902.
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The influence of estrogens on the lacrimal gland is very controversial. Some investigators have found that estrogens cause glandular regression, suppression of protein production and reduced tear secretion. Yet others have reported that estrogen deficiency leads to acinar cell necrosis, DNA degradation, inflammation, tissue loss and dry eye. To help clarify the impact of estrogens on the lacrimal gland, we examined the effect of complete estrogen absence on gene expression in lacrimal tissue. Our genetic focus was prompted by the recognition that estrogens act classically be regulating gene transcription.
Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice (n = 5/sex/group; n = 3 separate experiments). Aromatase, an enzyme, controls the formation of estrogens, and estrogen synthesis is completely eliminated in ArKO mice. Glands were pooled according to sex and group, processed for the purification of total RNA, and analyzed for differentially expressed mRNAs by using GE CodeLink Bioarrays (n ~ 20,000 genes/array). Array data were evaluated with GeneSifter bioinformatics software and statistical significance (p < 0.05) was determined by using the Student’s t-test. Gene expression was confirmed by the use of Affymetrix GeneChips.
Our results demonstrate that: [a] estrogen regulates the expression of over 1,100 genes in both male and female lacrimal tissues; [b] the nature of estrogen’s effect on gene expression is sex-dependent; [c] estrogen has a significant impact on numerous gene ontologies in lacrimal tissue. For example, estrogen presence stimulates genes associated with cellular metabolism, whereas its absence stimulates genes related to cellular biosynthesis; and [d] the complete lack of estrogen does not prevent the appearance of significant, sex-related differences in the expression of over 2,500 genes.
Our findings show that estrogens modulate the expression of many lacrimal gland genes. Our results also demonstrate that the lacrimal gland is functional in the absence of estrogen.
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