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Old 06-14-2018, 05:56 AM
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rss Androgens induce growth of the limb skeletal muscles in a rapamycin-insensitive manne

Androgens induce growth of the limb skeletal muscles in a rapamycin-insensitive manner.

Am J Physiol Regul Integr Comp Physiol. 2018 Jun 13;:

Authors: Rossetti ML, Fukuda DH, Gordon BS

Abstract
Signaling through the mechanistic target of rapamycin complex 1 (mTORC1) has been well-defined as an androgen-sensitive 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 weeks to induce atrophy of skeletal muscle. Then, castrated mice were implanted with either a control pellet or pellet that administered rapamycin (~2.5 mg/kg/day). Seven days post implant, 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 6-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 kD (Thr389) and uncoordinated like kinase 1 (Ser757). While castration reduced TA mass, muscle fiber cross sectional area, and total protein content, ND administration restored these measures to sham levels in a rapamycin-insensitive 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.


PMID: 29897818 [PubMed - as supplied by publisher]



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