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P. Khandelwal, S. Liu, D. A. Sullivan; Androgen Stimulation of Lipid-Related Genes in Human Meibomian Gland Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4158.
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Androgens significantly increase the transcription of lipid-related genes in non-ocular human sebaceous gland epithelial cells. This hormone action then leads to the generation of proteins that augment both the synthesis and secretion of lipids. We sought to determine whether androgens exert a similar effect on epithelial cells from the human meibomian gland, which is a large sebaceous gland. We also sought to determine whether this hormonal influence is unique, as compared to human conjunctival epithelial cells.
Immortalized human meibomian gland and conjunctival (gift from Dr. Ilene Gipson) epithelial cells were treated with placebo or physiological levels of dihydrotestosterone (DHT) for optimal time periods. Cells (n = 3 samples/treatment) were then processed for the generation of RNA and the analysis of mRNA levels by using Illumina humanHT-12 v3 expression BeadChips and Geospiza software.
Our results show that DHT has a significant impact on the expression of numerous genes related to lipid metabolic pathways in human meibomian gland epithelial cells. Androgen treatment stimulated 25 different ontologies (with ≥ 5 genes) involved with lipid biosynthesis, homeostasis, transport and binding, as well as with cholesterol, fatty acid, phospholipid and steroid dynamics. Androgen exposure also significantly increased the expression of ontologies (< 5 genes) associated with fatty acid elongation and phospholipid dephosphorylation, and with the activities of fatty-acyl-CoA synthase, 7-dehydrocholesterol reductase, C-3 sterol dehydrogenase, lathosterol oxidase, malate dehydrogenase, C-5 sterol desaturase and ATP citrate synthase. In contrast, DHT administration had minimal effect on lipid-related ontologies in human conjunctival epithelial cells.
Our findings demonstrate that the effect of DHT on meibomian gland epithelial cells is analogous to that of other sebaceous gland epithelial cells, and is not duplicated in human conjunctival epithelial cells. These results suggest that androgens may play a significant role in the regulation of lipid synthesis and secretion in the human meibomian gland in vivo.
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