Response of the adipose tissue transcriptome to dihydrotestosterone in mice

Androgens have been postulated to be important modulators of adipose tissue metabolism and fat cell function. In the present study, we investigated the response of male and female mice retroperitoneal adipose tissue to the non-aromatizable androgen dihydrotestosterone (DHT). Adipose tissue samples were obtained in gonadectomized (GDX) animals treated with vehicle (control group), or injected with 0.1mg DHT at 1, 3, 6, 12, 18 and 24h prior to necropsy. Transcripts which were significantly modulated were considered as androgen-responsive genes. Quantitative real-time RT-PCR was used to confirm results from the microarry analysis in a subset of 46 probe sets in male mice and 98 probe sets in female mice. Using both methods and considering peak time versus control, 74.5% and 61.2% of the modulated genes were confirmed by PCR in males and females, respectively. Four genes were significantly stimulated in a similar manner by DHT in both sexes, namely metallothionein 1 (Mt1), growth arrest and DNA-damage-inducible 45 gamma (Gadd45g), cyclin-dependent kinase inhibitor 1A (Cdkn1a), and fk506-binding protein 5 (Fkbp5). All these genes appear to be associated with a down-regulation of adipocyte differentiation/proliferation and adipogenesis. In conclusion, this study which evaluated the transcriptome response of adipose tissue to DHT in male and female mice suggests that DHT consistently modulates genes involved in the regulation of adipogenesis in retroperitoneal adipose tissue of both male and female animals.

16

Zhang Y, Calvo E, Martel C, Luu-The V, Labrie F, Tchernof A