Research

Hormonal

Muscle hypertrophy is driven by the PI3K-AKT-mTOR pathway, where IGF-1 and insulin signaling promote protein synthesis and inhibit degradation, while myostatin/activin signaling via Smad2/3 inhibits growth.

To build muscle, your body relies on specific hormonal signals like IGF-1 and insulin to activate the mTOR pathway, which drives protein synthesis and blocks breakdown. Conversely, myostatin acts as a brake on growth. Understanding this balance explains why resistance training (which stimulates these pathways) is effective, while conditions that elevate myostatin or impair insulin signaling can hinder growth.

StrongSupportsHIGH confidence
Insulin and insulin-like growth factor 1 (IGF1) are potent anabolic factors that sustain organism and muscle growth... This pathway regulates protein synthesis, protein degradation... The second major signaling pathway that controls skeletal muscle growth involves myostatin... induce phosphorylation of Smad2/3 to promote the formation of a heterotrimeric complex with Smad4
Roberta Sartori et al. · Nature Communications · 2021

Why this rating

Review of multiple genetic models (knockouts, transgenics) and pharmacological studies.

Source

Mechanisms of muscle atrophy and hypertrophy: implications in health and disease

Roberta Sartori et al. · Nature Communications · 2021

DOI 10.1038/s41467-020-20123-1

narrative_reviewCited 902×
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DOI resolved against Crossref · corpus check 2026-06-10

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