Gender difference of androgen actions on skeletal muscle transcriptome

Abstract

Sarcopenia is related to metabolic syndrome in postmenopausal women. Hormone replacement therapies with androgens improve muscle functions by molecular mechanisms that are still unknown, at least partly because the skeletal muscle transcriptome has been less characterized in females. We performed the serial analysis of gene expression method in six experimental groups, intact (male and female), ovariectomy (OVX), OVXCdihydrotestosterone (DHT) injection 1, 3, or 24 h before kill in mice. The 438 transcript species differentially expressed between gender showed that females had higher expression levels of mRNA related to cytoskeleton/contractile apparatus and mitochondrial processes as well as protein, lipid, and amino acid metabolisms. In females, OVX and DHT modulated 109 and 128 transcript species respectively. OVX repressed transcripts of fast/glycolytic fiber, glycolysis, and glucose transport, whereas all these effects were reversed 3 h after the DHT injection. Moreover, DHT treatment induced transcripts which reduce intracellular Ca 2C level at early time points. These results may suggest that DHT treatment in OVX mice increases muscle contractility by affecting fiber distribution and intracellular Ca 2C concentration as well as improving glucose metabolism. On the other hand, transcripts of fast/oxidative fiber, oxidative phosphorylation, and ATP production were repressed 24 h after DHT administration. In our previous study using male mice, transcripts in oxidative phosphorylation and ATP production were induced 24 h after DHT injection (Yoshioka M, Boivin A, Ye P, Labrie F & St-Amand J 2006 Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression. Journal of Molecular Endocrinology 36 247-259). These results demonstrate gender differences in DHT actions on skeletal muscle, and contribute to a precise understanding of the molecular mechanisms of androgen actions in the female skeletal muscle.

Gender dimorphism in the exercise-naïve murine skeletal muscle proteome

“…1), which could indicate a greater proportion of oxidative fiber types. This pattern is confirmed by the significantly decreased Troponin T3 fast transcription observed in female C57/BL6 murine gastrocnemius muscle by Yoshioka et al [5]. A greater proportion of oxidative fibers is consistent with the increased expression found for myoglobin in our female mice.…”

“…This trend is similar to the human vastus lateralis mRNA assay performed by Roth et al [6] in which they found more than three fourths of transcripts up-regulated in males, though the specific proteins are not similar to those presented here. Of interest is that three protein fragments identified here were found to have increased transcription by Yoshioka et al (ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit; Malate dehydrogenase 2, NAD [mitochondrial]; Aconitase 2, mitochondrial) [5], despite insignificant expression differences of the full-length protein between genders. This could indicate an increased turnover rate of these proteins in females when compared to males.…”

“…Of non-challenged muscle studies, two DNA microarray studies of skeletal muscle report conflicting results. Yoshioka et al [5] showed increased transcription of multiple myofibrillar and metabolic proteins in female murine gastrocnemius muscle with 80% of transcripts higher in females, while Roth et al [6] found differential transcription of roughly 200 genes in vastus lateralis muscle biopsies of adult men and women, 75% of which were higher in men, without a clear functional pattern. The inconsistency between the studies is likely due to procedural differences [5] or tissue.…”

“…Yoshioka et al [5] showed increased transcription of multiple myofibrillar and metabolic proteins in female murine gastrocnemius muscle with 80% of transcripts higher in females, while Roth et al [6] found differential transcription of roughly 200 genes in vastus lateralis muscle biopsies of adult men and women, 75% of which were higher in men, without a clear functional pattern. The inconsistency between the studies is likely due to procedural differences [5] or tissue. Regardless, mRNA levels are not always consistent with protein abundance [7] and cannot provide information regarding post-translational modifications, making it important to consider protein expression in addition to transcription.…”

<b>Time on feedlot and sexual effects on animal performance and characteristics of lamb’s meat

“…In the current study LMA increased in rams, which was expected. This increase may be due to muscle hypertrophy, stimulation by testosterone treatment in later postnatal periods, direct or indirect satellite cell proliferation or muscle protein synthesis (Yoshioka, Boivin, Bolduc, & St-Amand, 2007). According to Haddad, Husein, and Swedan (2006), there was no effect of castration in lambs for HCW, CCW, dressing percentage, or LMA.…”