Format

Send to

Choose Destination
J Steroid Biochem Mol Biol. 2013 Nov;138:152-61. doi: 10.1016/j.jsbmb.2013.05.005. Epub 2013 May 25.

Impaired hypertrophy in myoblasts is improved with testosterone administration.

Author information

1
Muscle Cellular and Molecular Physiology Research Group (MCMPRG), Institute of Sport and Physical Activity Research (ISPAR), University of Bedfordshire, UK; School of Health and Social Care, Bournemouth University, UK.

Abstract

We investigated the ability of testosterone (T) to restore differentiation in multiple population doubled (PD) murine myoblasts, previously shown to have a reduced differentiation in monolayer and bioengineered skeletal muscle cultures vs. their parental controls (CON) (Sharples et al., 2011, 2012 [7,26]). Cells were exposed to low serum conditions in the presence or absence of T (100nM)±PI3K inhibitor (LY294002) for 72h and 7 days (early and late muscle differentiation respectively). Morphological analyses were performed to determine myotube number, diameter (μm) and myonuclear accretion as indices of differentiation and myotube hypertrophy. Changes in gene expression for myogenin, mTOR and myostatin were also performed. Myotube diameter in CON and PD cells increased from 17.32±2.56μm to 21.02±1.89μm and 14.58±2.66μm to 18.29±3.08μm (P≤0.05) respectively after 72h of T exposure. The increase was comparable in both PD (+25%) and CON cells (+21%) suggesting a similar intrinsic ability to respond to exogenous T administration. T treatment also significantly increased myonuclear accretion (% of myotubes expressing 5+ nuclei) in both cell types after 7 days exposure (P≤0.05). Addition of PI3K inhibitor (LY294002) in the presence of T attenuated these effects in myotube morphology (in both cell types) suggesting a role for the PI3K pathway in T stimulated hypertrophy. Finally, PD myoblasts showed reduced responsiveness to T stimulated mRNA expression of mTOR vs. CON cells and T also reduced myostatin expression in PD myoblasts only. The present study demonstrates testosterone administration improves hypertrophy in myoblasts that basally display impaired differentiation and hypertrophic capacity vs. their parental controls, the action of testosterone in this model was mediated by PI3K/Akt pathway.

KEYWORDS:

Akt; Muscle stem cell; Myostatin; PI3K; Satellite cell; mTOR

PMID:
23714396
DOI:
10.1016/j.jsbmb.2013.05.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center