Androgens Induce Growth Of The Limb Skeletal Muscles In A Rapamycin-Insensitive Manner

Keywords

Hypogonadism; Muscle atrophy; Protein balance; Testosterone

Abstract

Signaling through the mechanistic target of rapamycin complex 1 (mTORC1) has been well defined as an androgensensitive transducer mediating skeletal muscle growth in vitro; however, this has yet to be tested in vivo. As such, male mice were subjected to either sham or castration surgery and allowed to recover for 7 wk to induce atrophy of skeletal muscle. Then, castrated mice were implanted with either a control pellet or a pellet that administered rapamycin (~2.5 mg·kg-1·day-1). Seven days postimplant, a subset of castrated mice with control pellets and all castrated mice with rapamycin pellets were given once weekly injections of nandrolone decanoate (ND) to induce muscle growth over a six-week period. Effective blockade of mTORC1 by rapamycin was noted in the skeletal muscle by the inability of insulin to induce phosphorylation of ribosomal S6 kinase 1 70 kDa (Thr389) and uncoordinated-like kinase 1 (Ser757). While castration reduced tibialis anterior (TA) mass, muscle fiber cross-sectional area, and total protein content, ND administration restored these measures to sham levels in a rapamycininsensitive manner. Similar findings were also observed in the plantaris and soleus, suggesting this rapamycin-insensitive effect was not specific to the TA or fiber type. Androgen-mediated growth was not due to changes in translational capacity. Despite these findings in the limb skeletal muscle, rapamycin completely prevented the ND-mediated growth of the heart. In all, these data indicate that mTORC1 has a limited role in the androgen-mediated growth of the limb skeletal muscle; however, mTORC1 was necessary for androgen-mediated growth of heart muscle.

Publication Date

10-1-2018

Publication Title

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volume

315

Issue

4

Number of Pages

R721-R729

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1152/AJPREGU.00029.2018

Socpus ID

85063764712 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85063764712

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