Ornithine Decarboxylase Is Upregulated by the Androgen Receptor in Skeletal Muscle and Regulates Myoblast Proliferation

    Nicole K. L. Lee, Jarrod P. Skinner, Jeffrey D. Zajac, Helen E. MacLean
    TLDR Androgens increase muscle mass by promoting myoblast growth through ornithine decarboxylase.
    The study found that ornithine decarboxylase 1 (Odc1) was regulated by the androgen receptor (AR) in skeletal muscle, with higher expression in adult male mice compared to females and younger males. Odc1 was essential for myoblast proliferation, as its inhibition reduced myoblast numbers, while overexpression increased them. AR deletion in mice led to decreased Odc1 expression, indicating direct regulation by AR. Dihydrotestosterone (DHT) also upregulated Odc1 in human myoblasts, supporting its role in proliferation. These findings suggested that androgens, through AR, contributed to greater muscle mass in males and normal muscle development, with potential therapeutic implications for enhancing muscle mass in conditions like HIV, cancer cachexia, and sarcopenia. ODC was already a target for treating hirsutism, indicating the potential for developing ODC agonists to increase muscle mass without androgen side effects.
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