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P. Khandelwal, S. Liu, D. A. Sullivan; Dihydrotestosterone Regulation of Androgen Receptor mRNA in Human Ocular Surface Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4266.
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Androgens are known to exert a significant influence on the structure and function of ocular surface epithelia. In addition, androgens have been proposed as a topical therapy for such conditions as corneal wound healing, meibomian gland dysfunction and evaporative dry eye. However, the mechanism(s) underlying these androgen-eye interactions are unclear. We hypothesize that androgen action is mediated primarily through androgen receptors (AR) in epithelial cells, leading to an altered expression of specific genes and proteins. To begin to test this hypothesis, we examined whether androgens regulate AR mRNA levels in human corneal, conjunctival and meibomian gland epithelial cells. The AR, at least in non-ocular epithelia, is a classic target for androgen autoregulation.
Immortalized human meibomian gland and prostate (LNCaP; ATCC) epithelial cells, immortalized corneal and conjunctival epithelial cells (gift from Ilene Gipson, USA), and primary corneal epithelial cells (gift from James Chodosh, USA) were grown in keratinocyte serum free or RPMI media until reaching about 80% confluence. Cells (n = 3 wells/treatment/experiment) were then incubated with either vehicle or 10 nM dihydrotestosterone (DHT) for up to 5 days. At designated times cells were processed for total RNA isolation and analysis of AR mRNA by real time PCR.
Our results show that the DHT induces a marked, time-dependent decrease in AR mRNA levels in immortalized human corneal, conjunctival and meibomian gland epithelial cells. This androgen effect, which was not observed in sham-treated controls, became increasingly prominent after 48 hours of hormone exposure. This DHT influence in immortalized cells was analogous to that found in LNCaP cells. In contrast, DHT caused a marked, time-dependent increase in AR mRNA content in primary corneal epithelial cells.
These findings support our hypothesis that androgen action in ocular surface epithelial cells involves an alteration in gene expression. Our results also suggest that androgen receptors may play a central role in this androgen activity.
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