Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression

Abstract

In order to characterize the action of androgen in skeletal muscle, we have investigated the effects of castration (GDX) and dihydrotestosterone (DHT) on global gene expression in mice. The serial analysis of gene expression method was performed in the muscle of male mice in six experimental groups: intact, GDX and GDX+DHT injection 1, 3, 6 or 24 h before they were killed. A total of 780 822 sequenced tags quantified the expression level of 80 142 tag species. Thirteen and seventy-nine transcripts were differentially expressed in GDX and DHT respectively (P,0·05), including eight partially characterized and 21 potential novel transcripts. The induced transcripts within 3 h after DHT injection were involved in the following functions: transcription, protein synthesis, modification and degradation, muscle contraction and relaxation, cell signaling, polyamine biosynthesis, cell cycle progression and arrest, angiogenesis, energy metabolism and immunity. However, the inductions of transcripts related to cell cycle arrest and angiogenesis were no longer significant 24 h after DHT injection. The current study might suggest that DHT promotes protein synthesis, cell signaling, cell proliferation and ATP production, as well as muscle contraction and relaxation at the transcriptional level in skeletal muscle in vivo.

Gender difference of androgen actions on skeletal muscle transcriptome

“…We have already reported that DHT injection into GDX male mice immediately induces transcripts related to power generation, protein synthesis, mitochondrial function, and satellite cells/myoblasts proliferation, in which only transcripts related to protein synthesis have been repressed at late time point (Yoshioka et al 2006). In the present study, DHT injection into female GDX mice increased contractility as well as glucose transport and glycogenolysis/glycolysis at the transcriptional level.…”

“…The common functional regulation by DHT in the female mice of the present study and male mice of our previous studies (Yoshioka et al 2006) was an induction of transcripts involved in muscle relaxation at early time points, although male mice have shown concomitant increase in transcripts related to muscle contraction. The main difference between male and female mice in response to DHT injection was seen in transcripts related to mitochondrial function.…”

“…We also included our previous study of male mice (Yoshioka et al 2006) in order to compare gender differences of DHT action. Both male and female mice were purchased at the same time.…”

“…Skeletal muscle fibers contain high levels of both contractile proteins and ATP-producing metabolic enzymes (Yoshioka et al 2003(Yoshioka et al , 2006, which together make possible the extremely high-energy flux of actively exercising muscle. Moreover, muscle fibers are biochemically and physiologically specialized with different fibers expressing functionally distinct contractile protein isoforms and different relative amounts of oxidative versus glycolytic metabolic enzymes (Bottinelli & Reggiani 2000), which are closely related to the occurrence of obesity and insulin resistance (Lillioja et al 1987, Tanner et al 2002.…”

“…Therefore, in order to gain insights into the molecular mechanisms of androgen actions on skeletal muscle in postmenopausal women, we have investigated the effect of ovariectomy (OVX) and DHT on global gene expression in gastrocnemius muscle of female mice. Moreover, the results are reanalyzed and compared with our previous study in male mice (Yoshioka et al 2006).…”