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J Appl Physiol (1985). 2016 Mar 15;120(6):592-8. doi: 10.1152/japplphysiol.00874.2015. Epub 2016 Jan 14.

Paracrine and endocrine modes of myostatin action.

Author information

1
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland sjlee@jhmi.edu.

Abstract

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit muscle mass. In adult animals, MSTN is made almost exclusively by skeletal muscle and circulates in the blood. A critical question is whether this circulating MSTN protein can enter the active pool to regulate muscle growth or whether all of the activity of MSTN results from locally produced protein. Here, we addressed this question in mice by using a Cdx2-Cre transgene in conjunction with a conditional Mstn-flox allele to generate mice in which Mstn was targeted in a regionally restricted manner. Specifically, we generated mosaic mice in which MSTN production was eliminated in posteriorly located muscles but not in anteriorly located muscles, resulting in mice in which circulating levels of MSTN were reduced roughly by half. Analysis of posteriorly located vs. anteriorly located muscles of these mice revealed clear differential effects indicative of an important paracrine role for MSTN in regulating muscle mass. Significant, albeit more subtle, effects consistent with an endocrine mode of MSTN action were also seen in these mice. These findings have important implications not only for the understanding of the physiological control of muscle mass but also for therapeutic strategies to target MSTN to treat patients with muscle loss.

KEYWORDS:

endocrine; myostatin; paracrine; skeletal muscle

PMID:
26769954
PMCID:
PMC4796182
DOI:
10.1152/japplphysiol.00874.2015
[Indexed for MEDLINE]
Free PMC Article

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