Sheep recombinant IGF-1 promotes organ-specific growth in fetal sheep.
Stremming. J J; White. A A; Donthi. A A; Batt. D G DG; Hetrick. B B; Chang. E I EI; Wesolowski. S R SR; Seefeldt. M B MB; McCurdy. C E CE; Rozance. P J PJ; Brown. L D LD
Key Findings
- oIGF‑1 boosts fetal organ growth (heart, kidney, spleen, adrenal)
- It increases skeletal muscle cell proliferation without increasing muscle mass or protein synthesis rate
- IGFBP‑1 to‑3 levels stay the same, meaning normal regulation isn’t disrupted
Practical Outcomes
- For biohackers, this study suggests that simply adding IGF‑1 (or a species‑specific version) is unlikely to bulk up adult muscle, though it may affect organ growth. It also shows that targeting IGF‑1 pathways won’t necessarily override the body’s natural binding‑protein controls, so any dosing protocols should be approached cautiously and expect limited muscle‑mass benefits.
Summary
A sheep‑specific version of IGF‑1 (oIGF‑1) was given to unborn sheep and it made certain organs like the heart and kidneys grow bigger and increased muscle‑cell activity, but it didn’t make the overall muscle bigger or speed up protein building in the muscle. The hormone behaved similarly to the human version in terms of not changing the body’s natural IGF‑binding proteins.
Abstract
IGF-1 is a critical fetal growth-promoting hormone. Experimental infusion of an IGF-1 analog, human recombinant LR3 IGF-1, into late gestation fetal sheep increased fetal organ growth and skeletal muscle myoblast proliferation. However, LR3 IGF-1 has a low affinity for IGF binding proteins (IGFBP), thus reducing physiologic regulation of IGF-1 bioavailability. The peptide sequences for LR3 IGF-1 and sheep IGF-1 also differ. To overcome these limitations with LR3 IGF-1, we developed an ovine (sheep) specific recombinant IGF-1 (oIGF-1) and tested its effect on growth in fetal sheep. First, we measured <i>in vitro</i> myoblast proliferation in response to oIGF-1. Second, we examined anabolic signaling pathways from serial skeletal muscle biopsies in fetal sheep that received oIGF-1 or saline infusion for 2 hours. Finally, we measured the effect of fetal oIGF-1 infusion versus saline infusion (SAL) for 1 week on fetal body and organ growth, <i>in vivo</i> myoblast proliferation, skeletal muscle fractional protein synthetic rate, <i>IGFBP</i> expression in skeletal muscle and liver, and IGF-1 signaling pathways in skeletal muscle. Using this approach, we showed that oIGF-1 stimulated myoblast proliferation <i>in vitro</i>. When infused for 1 week, oIGF-1 increased organ growth of the heart, kidney, spleen, and adrenal glands and stimulated skeletal myoblast proliferation compared to SAL without increasing muscle fractional synthetic rate or hindlimb muscle mass. Hepatic and muscular gene expression of <i>IGFBPs one to three</i> was similar between oIGF-1 and SAL. We conclude that oIGF-1 promotes tissue and organ-specific growth in the normal sheep fetus.
Study Information
pubmed
2022
2022-08-25T00:00:00.000Z
10.3389/fphys.2022.954948
4
59