Understand the source comparison
Systemic IGF-1 versus local mechano-growth factor
When GH reaches the liver, it binds the GH receptor and, via JAK2/STAT5 signaling, drives hepatic transcription of IGF-1. This liver-derived IGF-1 circulates (largely bound to IGFBP-3 and the acid-labile subunit) and accounts for most of the IGF-1 measured in
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- When GH reaches the liver, it binds the GH receptor and, via JAK2/STAT5 signaling, drives hepatic transcription of IGF-1. This liver-derived IGF-1 circulates (largely bound to IGFBP-3 and the acid-labile subunit) and accounts for most of the IGF-1 measured in blood. But skeletal muscle also produces IGF-1 locally, and mechanical loading favors a splice variant sometimes called mechano-growth factor (MGF, IGF-1Ec). The distinction matters: circulating IGF-1 provides a permissive anabolic background, whereas locally expressed IGF-1 acts in an autocrine/paracrine fashion right where mechanical damage and remodeling are occurring. Secretagogues raise systemic GH and therefore systemic IGF-1; they do not by themselves supply the mechanical stimulus that drives the local, load-specific IGF-1 response — which is one reason exercise is treated as the indispensable partner variable in any serious discussion of muscle outcomes.