Androgen Control of Human Corneal Epithelial Cells

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Androgen Control of Human Corneal Epithelial Cells
Payal Khandelwal and David A. Sullivan
Schepens Eye Research Institute and Harvard
Medical School, Boston, MA
The authors have no financial interest in the
subject matter of this poster.
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Purpose

• Androgens have been reported to correct defects,
  facilitate wound healing, suppress angiogenesis
  and stimulate mitosis in the corneal epithelium.
• We hypothesize that these hormone actions involve
  the regulation of gene expression, and tested
  this hypothesis in the current study.

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Methods

• Primary human corneal epithelial cells were
  treated with dihydrotestosterone (DHT) or placebo
  and then processed for the analysis of gene
  expression with Illumina humanHT-12 v3 expression
  BeadChips and BeadStudio and Geospiza software.

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Results

• DHT significantly influenced the expression of
  over 1,500 genes in primary human corneal
  epithelial cells.
• For example, androgen exposure upregulated genes
  encoding S100 calcium binding protein P
  (modulates tumorigenesis and cell cycle
  progression), syntenin (regulates transmembrane
  receptor trafficking, tumour cell metastasis,
  neuronal synapse function and NF-kappaB
  activation pathways), decorin (inhibits
  angiogenesis) and vimentin (helps maintain cell
  integrity) Table 1.

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Table 1 List of some of the genes upregulated in
primary human corneal epithelial cells by
androgen exposure
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Results

• Androgen exposure suppressed genes producing
  tubulins (promote angiogenesis), thrombospondin1
  (influence angiogenesis and tumorigenesis),
  keratin 3 (involved with corneal dystrophy) and
  matrix metallopeptidase 9 (degrades collagens)
  Table 2.
• DHT treatment also exerted a significant impact
  on many ontologies, including oxidative
  phosphorylation, transmembrane ion transport and
  cellular localization.

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Table 2 List of some of the genes downregulated
in primary human corneal epithelial cells by
androgen exposure
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Conclusion

• DHT regulates the expression of numerous genes
  which may play a role in corneal health and
  disease. Analysis of these genes and ontologies
  may provide insights into the mechanism(s) of
  androgen action on the corneal epithelium.