Androgen control of gene expression in the mouse meibomian gland.
OBJECTIVE
In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study's purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression.


METHODS
Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA).


RESULTS
The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes.


CONCLUSIONS
These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.
Schirra
Frank
F
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Suzuki
Tomo
T
Richards
Stephen M
SM
Jensen
Roderick V
RV
Liu
Meng
M
Lombardi
Michael J
MJ
Rowley
Patricia
P
Treister
Nathaniel S
NS
Sullivan
David A
DA
D000818:Animals; D005136:Eye Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008537:Meibomian Glands / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation
D005136:Eye Proteins; D012333:RNA, Messenger; D013739:Testosterone