Selective androgen receptor modulator, S42 has anabolic and anti-catabolic effects on cultured myotubes

Area of Science:

• Biochemistry
• Molecular Biology
• Muscle Physiology

Background:

• Selective androgen receptor modulators (SARMs) are investigated for therapeutic potential.
• S42, a novel SARM, demonstrates beneficial lipid metabolism and muscle effects without prostate stimulation.
• Previous studies indicated S42 increases levator ani muscle weight in orchiectomized rats.

Purpose of the Study:

• To investigate the direct effects of S42 on cultured C2C12 myotubes.
• To elucidate the molecular mechanisms underlying S42's potential anabolic and anti-catabolic actions in skeletal muscle.

Main Methods:

• Real-time PCR to quantify gene expression levels of atrogin1 and MuRF1.
• Western blotting or similar techniques to assess protein phosphorylation status of p70S6K and Akt.
• Treatment with S42, insulin, rapamycin, and potentially IGF-1 in C2C12 myotube cultures.

Main Results:

• S42 significantly reduced expression of atrogin1 and MuRF1, key muscle atrophy-related genes.
• S42 increased phosphorylation of p70S6K, a protein synthesis promoter, comparable to insulin.
• This p70S6K activation was blocked by rapamycin, indicating mTORC1 pathway involvement.
• S42 did not alter Akt phosphorylation or increase IGF-1 mRNA levels.
• S42 inhibited muscle degradation pathways and activated protein synthesis signaling.

Conclusions:

• S42 exhibits anti-catabolic effects by inhibiting the muscle degradation pathway.
• S42 demonstrates anabolic effects via mTORC1-p70S6K signaling activation, independent of IGF-1-Akt.
• S42 presents a potential therapeutic agent for muscle wasting conditions.