Androgens affect myogenesis In Vitro and increase local IGF-1 expression

Nick Sculthorpe, Andrew M. Solomon, Andrea C. M. Sinanan, Pierre-Marc G. Bouloux, Fergal Grace, Mark P. Lewis

Research output: Contribution to journalArticle

Abstract

Androgens Affect Myogenesis In Vitro and Increase Local Insulin-Like Growth Factor I Expression. Med. Sci. Sports Exerc., Vol. 44, No. 4, pp. 610-615, 2012. 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) I. 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(-1)) 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.
Original languageEnglish
Pages (from-to)610-615
Number of pages6
JournalMedicine & Science in Sports & Exercise
Volume44
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Keywords

  • MUSCLE CELL DIFFERENTIATION
  • MOLECULAR PHYSIOLOGY
  • TESTOSTERONE
  • INSULIN-LIKE GROWTH FACTOR 1

Cite this

Sculthorpe, Nick ; Solomon, Andrew M. ; Sinanan, Andrea C. M. ; Bouloux, Pierre-Marc G. ; Grace, Fergal ; Lewis, Mark P. / Androgens affect myogenesis In Vitro and increase local IGF-1 expression. In: Medicine & Science in Sports & Exercise. 2012 ; Vol. 44, No. 4. pp. 610-615.
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abstract = "Androgens Affect Myogenesis In Vitro and Increase Local Insulin-Like Growth Factor I Expression. Med. Sci. Sports Exerc., Vol. 44, No. 4, pp. 610-615, 2012. 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) I. 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(-1)) 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.",
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Androgens affect myogenesis In Vitro and increase local IGF-1 expression. / Sculthorpe, Nick; Solomon, Andrew M.; Sinanan, Andrea C. M.; Bouloux, Pierre-Marc G.; Grace, Fergal; Lewis, Mark P.

In: Medicine & Science in Sports & Exercise, Vol. 44, No. 4, 04.2012, p. 610-615.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Androgens affect myogenesis In Vitro and increase local IGF-1 expression

AU - Sculthorpe, Nick

AU - Solomon, Andrew M.

AU - Sinanan, Andrea C. M.

AU - Bouloux, Pierre-Marc G.

AU - Grace, Fergal

AU - Lewis, Mark P.

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N2 - Androgens Affect Myogenesis In Vitro and Increase Local Insulin-Like Growth Factor I Expression. Med. Sci. Sports Exerc., Vol. 44, No. 4, pp. 610-615, 2012. 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) I. 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(-1)) 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.

AB - Androgens Affect Myogenesis In Vitro and Increase Local Insulin-Like Growth Factor I Expression. Med. Sci. Sports Exerc., Vol. 44, No. 4, pp. 610-615, 2012. 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) I. 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(-1)) 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.

KW - MUSCLE CELL DIFFERENTIATION

KW - MOLECULAR PHYSIOLOGY

KW - TESTOSTERONE

KW - INSULIN-LIKE GROWTH FACTOR 1

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M3 - Article

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