Myocytic androgen receptor controls the strength but not the mass of limb muscles

Céline Chambon1, Delphine Duteil, Alban Vignaud

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, Collège de France, 67404 Illkirch, France. chambon@igbmc.fr

Insights

Androgens impact muscle growth differently depending on the muscle type. The androgen receptor (AR) in muscle cells is crucial for perineal muscle growth but not limb muscle growth, though it affects muscle strength.

Area of Science:

  • Muscle physiology
  • Endocrinology
  • Molecular biology

Background:

  • Androgens are known to promote skeletal muscle growth, but the precise mechanisms and receptor involvement remain unclear.
  • The androgen receptor (AR) is a key mediator of androgen action, belonging to the nuclear receptor superfamily.

Purpose of the Study:

  • To investigate the specific role of the androgen receptor (AR) in myofibers for mediating androgen effects on skeletal muscle.
  • To differentiate androgen signaling pathways in various skeletal muscle types.

Main Methods:

  • Generation of mice with selective ablation of the AR in myofibers.
  • Analysis of androgen-induced gene expression (IGF-IEa) and muscle hypertrophy in perineal and limb muscles.
  • Assessment of muscle strength and myofibrillar organization in AR-deficient mice.

Main Results:

  • Myocytic AR controls androgen-induced IGF-IEa expression and postnatal hypertrophy in perineal muscles.
  • Postnatal hypertrophy of limb muscles in response to androgens is independent of myocytic AR.
  • AR deficiency in limb myocytes impairs sarcomere organization and reduces muscle strength.

Conclusions:

  • Androgens regulate perineal and limb muscle mass through distinct AR-dependent and AR-independent pathways.
  • Myocytic AR plays a critical role in maintaining myofibrillar organization and muscle force production.
  • Distinct androgen signaling mechanisms offer potential for developing targeted therapies for muscle strength modulation.

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