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Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice

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Abstract

Purpose

The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model.

Methods

We examined the effects of Orx either with or without testosterone (T) or estradiol (E2) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice.

Results

Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E2 administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E2, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx.

Conclusions

The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.

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Acknowledgments

This work was supported by a starting grant (to WD) from the Special Research Fund (BOF-UGent) and by a research grant from the Research Foundation-Flanders (FWO). Y Taes is a postdoctoral fellow of the Research Foundation-Flanders (FWO). SL is supported by an Alfred Deakin Post-Doctoral Research Fellowship.

Conflict of interest

All authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Movement and Sports Sciences, Ghent University, Watersportlaan 2, 9000, Ghent, Belgium

    H. De Naeyer, I. Everaert & W. Derave

  2. Centre for Physical Activity and Nutrition Research, Deakin University, Burwood, Australia

    S. Lamon & A. P. Russell

  3. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

    A. De Spaey & Y. Taes

  4. Department of Basic Medical Sciences, Division Physiology, Ghent University, Ghent, Belgium

    B. Vanheel

Authors
  1. H. De Naeyer
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  2. S. Lamon
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  3. A. P. Russell
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  4. I. Everaert
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  5. A. De Spaey
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  6. B. Vanheel
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  7. Y. Taes
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  8. W. Derave
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Corresponding author

Correspondence to W. Derave.

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Communicated by Martin Flueck.

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De Naeyer, H., Lamon, S., Russell, A.P. et al. Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice. Eur J Appl Physiol 114, 751–761 (2014). https://doi.org/10.1007/s00421-013-2800-y

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  • DOI: https://doi.org/10.1007/s00421-013-2800-y

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