Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy

Davis A. Englund; Bailey D. Peck; Kevin A. Murach; Ally C. Neal; Hannah A. Caldwell; John J. McCarthy; Charlotte A. Peterson; Esther E. Dupont-Versteegden

doi:10.1152/ajpcell.00260.2019

Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy

Davis A. Englund, Bailey D. Peck, Kevin A. Murach, Ally C. Neal, Hannah A. Caldwell, John J. McCarthy, Charlotte A. Peterson, Esther E. Dupont-Versteegden

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion. Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden (https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells/).

Original language	English
Pages (from-to)	C719-C724
Journal	American Journal of Physiology - Cell Physiology
Volume	317
Issue number	4
DOIs	https://doi.org/10.1152/ajpcell.00260.2019
State	Published - 2019

Bibliographical note

Funding Information:
This work was supported by funds from the Endowed University Professorship in Health Sciences, University of Kentucky, and NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR060701 to C. A. Peterson and J. J. McCarthy and Grant AR071753 to K. A. Murach. The project described was also supported by NIH National Center for Advancing Translational Sciences through Grant TL1 TR001997 (to D. A. Englund).

Publisher Copyright:
Copyright © 2019 the American Physiological Society

Keywords

Hypertrophy
Satellite cell
Skeletal muscle
Stem cell
Testosterone

ASJC Scopus subject areas

Physiology
Cell Biology

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10.1152/ajpcell.00260.2019

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title = "Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy",

abstract = "It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion. Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden (https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells/).",

keywords = "Hypertrophy, Satellite cell, Skeletal muscle, Stem cell, Testosterone",

author = "Englund, {Davis A.} and Peck, {Bailey D.} and Murach, {Kevin A.} and Neal, {Ally C.} and Caldwell, {Hannah A.} and McCarthy, {John J.} and Peterson, {Charlotte A.} and Dupont-Versteegden, {Esther E.}",

note = "Funding Information: This work was supported by funds from the Endowed University Professorship in Health Sciences, University of Kentucky, and NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR060701 to C. A. Peterson and J. J. McCarthy and Grant AR071753 to K. A. Murach. The project described was also supported by NIH National Center for Advancing Translational Sciences through Grant TL1 TR001997 (to D. A. Englund). Publisher Copyright: Copyright {\textcopyright} 2019 the American Physiological Society",

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AU - Englund, Davis A.

AU - Peck, Bailey D.

AU - Murach, Kevin A.

AU - Neal, Ally C.

AU - Caldwell, Hannah A.

AU - McCarthy, John J.

AU - Peterson, Charlotte A.

AU - Dupont-Versteegden, Esther E.

N1 - Funding Information: This work was supported by funds from the Endowed University Professorship in Health Sciences, University of Kentucky, and NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR060701 to C. A. Peterson and J. J. McCarthy and Grant AR071753 to K. A. Murach. The project described was also supported by NIH National Center for Advancing Translational Sciences through Grant TL1 TR001997 (to D. A. Englund). Publisher Copyright: Copyright © 2019 the American Physiological Society

PY - 2019

Y1 - 2019

N2 - It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion. Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden (https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells/).

AB - It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion. Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden (https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells/).

KW - Hypertrophy

KW - Satellite cell

KW - Skeletal muscle

KW - Stem cell

KW - Testosterone

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ER -

Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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