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Androgens affect myogenesis in vitro and increase local IGF-1 expression

journal contribution
posted on 11.09.2014, 15:05 by Nicholas Sculthorpe, Andrew M. Solomon, Andrea C.M. Sinanan, Pierre-Marc G. Bouloux, Fergal Grace, Mark LewisMark Lewis
Purpose: The mechanism whereby anabolic androgens are associated with hypertrophy of skeletal muscle is incompletely understood but may involve an interaction with locally generated insulin-like growth factor (IGF) 1. The present investigation utilized a cell culture model of human skeletal muscle-derived cell maturation to test the hypothesis that androgens increase differentiation of human muscle precursor cells in vitro and to assess effects of androgen with or without IGF-1 on IGF-1 messenger RNA (mRNA) expression in human muscle precursor cells. Methods: Differentiation of muscle-derived cells was induced under standard low-serum conditions. Cultures were then exposed to androgen (testosterone (T)) at 50, 100, and 500 nM or IGF-1 (10-50 ng•mL ). Immunocytochemistry and real-time polymerase chain reaction (RT-PCR) were used to assess effects of androgens and IGF-1 after 3-(early) or 7-d (late) muscle differentiation, respectively; RT-PCR was used to quantify the effects on androgen receptor expression. Results: Under low-serum conditions, 3-d exposure to androgens or IGF-1 or both resulted in no significant increase in cellular myogenic commitment. After 7-d exposure, however, T and IGF-1 were both found to increase fusion index with no observable synergistic effect. T also increased IGF-1 mRNA generation (P < 0.0001), whereas exogenous IGF-1 (P < 0.001) reduced IGF-1 mRNA transcription relative to control. The T effect was reversible after treatment with flutamide, an androgen receptor antagonist. Conclusions: Both T and IGF-1 increase myogenic commitment after 7-d exposure to a differentiation medium. With T causing a concomitant increase in IGF-1 mRNA underpinning IGF-1 as a central mediator in the cellular pathways associated with muscle hypertrophy, including those affected by androgens. The novel system described has the potential for elucidating the pattern of growth factor effects associated with androgens in skeletal muscle. © 2012 by the American College of Sports Medicine.

Funding

This work was supported by the Ipsen Fund, the Society for Endocrinology (A.M.S.), the Wellcome Trust, the Eastman Foundation for Oral Research and Training (M.P.L.), and University College London (P.B.M.G.).

History

School

  • Sport, Exercise and Health Sciences

Published in

Medicine and Science in Sports and Exercise

Volume

44

Issue

4

Pages

610 - 615

Citation

SCULTHORPE, N. ... et al., 2012. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Medicine and Science in Sports and Exercise, 44 (4), pp. 610 - 615.

Publisher

© American College of Sports Medicine

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2012

Notes

Closed access.

ISSN

0195-9131

eISSN

1530-0315

Language

en

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