Transcriptomic characterization of the long-term dihydrotestosterone effects in adipose tissue.
OBJECTIVE
To study the long-term transcriptomic effects of dihydrotestosterone (DHT) in adipose tissue. Fat distribution is regulated by sexual hormones. It is still unclear if androgens are promoting or reducing intra-abdominal fat accumulation.


METHODS
Retroperitoneal adipose tissue were isolated from each group of gonadectomized (GDX) C57BL6 male mice treated with vehicle or DHT for 21 days. Serial analysis of gene expression (SAGE) was performed to generate approximately 150,000 SAGE tags from each sample.


RESULTS
Among the numerous genes regulated by DHT, transcripts involved in glycolysis, such as aldolase 1 A isoform and pyruvate kinase muscle as well as lipogenic transcripts, such as malic enzyme supernatant and ELOVL family member 6 elongation of long chain fatty acids were down-regulated by androgen supplementation. In contrast, transcripts involved in lipolysis and fatty acid oxidation, such as carboxylesterase 3, acetyl-coenzyme A acyltransferase 1, 3-ketoacyl-CoA thiolase B and enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A dehydrogenase were up-regulated by DHT. Pro-apoptotic transcripts such as cell death-inducing DFFA-like effector c, BCL2/adenovirus E1B 19 kDa-interacting protein 1 NIP3 and -interacting protein 3-like were up-regulated by DHT, whereas transcripts involved in promotion of cell cycle such as cyclin D2 were down-regulated by DHT.


CONCLUSIONS
These results suggest that chronic androgen treatment may help to improve metabolic profile by regulating various critical pathways involved in adipose tissue physiology. In addition, several genes associated with a healthier metabolic profile, such as adiponectin and CD36 antigen, were up-regulated by 21 days of DHT treatment.
Bolduc
Carl
C
Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, 2705 Boulevard Laurier, Quebec City, Quebec, G1V 4G2 Canada.
Yoshioka
Mayumi
M
St-Amand
Jonny
J
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000235:genetics; D008291:Malate Dehydrogenase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D011770:Pyruvate Kinase / Q000235:genetics; D014158:Transcription, Genetic
D013196:Dihydrotestosterone; D008291:Malate Dehydrogenase; D011770:Pyruvate Kinase; D005634:Fructose-Bisphosphate Aldolase