MGF (Mechano Growth Factor)

Also known as: Mechano growth factor, IGF-1Ec (human), IGF-1Eb (rodent), IGF-1 E-peptide, MGF E-domain peptide

Research / Investigational only

not approved; mechano growth factors explicitly prohibited by WADA

4 notable studies · 5 references

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TLDR

MGF (mechano growth factor) is an IGF-1 gene splice variant, and a synthetic peptide from its unique C-terminal E-domain, that muscle produces more of after stretch or exercise (less so with age); the originating lab reported myoblast effects, but independent pharmaceutical-industry testing found none, there are no human trials, and WADA prohibits it.

At a Glance

Classification: Splice variant of the insulin-like growth factor 1 (IGF1) gene and its 24-amino-acid C-terminal E-domain peptide; proposed local (autocrine/paracrine) muscle-repair signal; receptor not identified

MGF (mechano growth factor) is the name a UK research group gave to a version of the IGF-1 gene product that muscle makes after stretch, overload or damage. The IGF-1 gene can be spliced in different ways. One version (IGF-1Ec in humans, called IGF-1Eb in rodents) ends in a distinct C-terminal "E-peptide". "MGF" refers both to that splice-variant mRNA and to a synthetic 24-amino-acid peptide made from its E-domain. Evidence is mixed: • Muscle stretch and resistance exercise increase MGF mRNA in animals and young people • The original lab reported that the synthetic E-peptide boosted myoblast proliferation • Researchers at two pharmaceutical companies could not reproduce any effect of the MGF peptide on myoblasts or muscle stem cells. There are no human trials of MGF peptide. It is not approved, and WADA specifically lists mechano growth factors as prohibited.

What Is MGF (Mechano Growth Factor)?

IGF-1Ea → the main IGF-1 splice form; produces mature IGF-1 plus the Ea peptide IGF-1Ec (human) / IGF-1Eb (rodent) = "MGF" → produces mature IGF-1 plus a distinct E-peptide MGF peptide (research market) → synthetic 24-amino-acid E-domain peptide, often with modifications for stability PEG-MGF → PEGylated version of the synthetic peptide designed to last longer Mature IGF-1 is the same 70-amino-acid hormone regardless of splice form; the debate is about whether the E-peptide has its own activity.

What Are Researchers Studying?

Mechanical loading of muscle

In rabbit muscle, stretch and especially stretch combined with electrical stimulation strongly increased both IGF-1 splice forms, including MGF.

Myoblast proliferation

In a cell model, the MGF E-domain peptide increased myoblast proliferation and delayed terminal differentiation, apparently through a receptor other than the IGF-1 receptor.

Aging muscle

After a bout of heavy knee-extensor exercise, MGF mRNA rose in the muscle of young men but not older men, while IGF-1Ea did not change in either group. Resting MGF levels were about 100-fold lower than IGF-1Ea.

Reproducibility

Using concentrations up to 500 ng/mL, researchers from two pharmaceutical companies found that MGF peptide did not increase proliferation of C2C12 cells, primary human myoblasts or mouse muscle stem cells and did not inhibit differentiation, whereas mature IGF-1 and full-length IGF-1Eb did. A 2010 review pointed out that no natural peptide matching synthetic MGF had ever been identified in or isolated from cultured cells, animal tissues or body fluids, so effects of the synthetic peptide should be kept separate from what the IGF-1 gene actually produces.

How Does It Work?

Proposed (contested) model: mechanical load or muscle damage ↓ alternative splicing of the IGF1 gene toward IGF-1Ec/Eb ("MGF") ↓ mature IGF-1 (acts on IGF-1 receptor) + a distinct E-peptide ↓ E-peptide proposed to activate satellite-cell / myoblast proliferation through an unidentified receptor ↓ local muscle repair. The splicing response is reasonably established. Independent activity of the synthetic E-peptide is not.

What Does the Research Show?

Human research

LIMITED and indirect. Human data show changes in MGF mRNA after exercise (and a blunted response with age). No human study has given MGF peptide.

Animal research

LIMITED: rabbit and rodent expression studies after stretch, overload and injury.

In-vitro research

CONFLICTING: the originating lab reported proliferative effects; an independent industry replication found none.

Notable Studies

Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation

animal

McKoy G, Ashley W, Mander J, et al. · 1999

Journal: Journal of Physiology. In rabbit muscle, stretch through limb immobilization markedly increased both IGF-1 splice forms (including MGF) within four days, and stretch combined with 10 Hz electrical stimulation increased them further.

Limitations: Measures mRNA, not protein or function; rabbit model.

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Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation

in-vitro

Yang SY, Goldspink G · 2002

Journal: FEBS Letters. In a myoblast cell model, the MGF E-domain peptide increased proliferation and inhibited terminal differentiation, unlike mature IGF-1. Blocking the IGF-1 receptor did not prevent this, suggesting a different receptor.

Limitations: Single cell model from the originating lab; not reproduced in later independent testing.

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Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise

human

Hameed M, Orrell RW, Cobbold M, et al. · 2003

Journal: Journal of Physiology. Eight young and seven older men did one bout of heavy single-leg knee-extension exercise. MGF mRNA rose in the young but not the old; IGF-1Ea mRNA did not change. Resting MGF mRNA was about 100-fold lower than IGF-1Ea.

Limitations: Small sample; one exercise bout; mRNA only; no MGF administered.

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Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells

in-vitro

Fornaro M, Hinken AC, Needle S, et al. · 2014

Journal: American Journal of Physiology - Endocrinology and Metabolism. Independent testing at two pharmaceutical companies found that MGF peptide up to 500 ng/mL did not increase proliferation of C2C12 cells, primary human myoblasts or primary mouse muscle stem cells and did not inhibit differentiation, while mature IGF-1 and full-length IGF-1Eb did.

Limitations: Cell-culture only; does not exclude effects in vivo or of other peptide variants.

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What We Still Don't Know

• Whether a free MGF E-peptide actually exists in the body (none has been isolated) • Whether the E-peptide has any biological activity of its own (studies conflict) • What receptor, if any, mediates proposed E-peptide effects • Whether synthetic MGF or PEG-MGF has any effect on human muscle (no human trials) • Stability and half-life of the native peptide in the body • Safety of research-market MGF products

Related Compounds

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Sources & References

  1. McKoy G et al. Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. Journal of Physiology. 1999.
  2. Yang SY et al. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Letters. 2002.
  3. Hameed M et al. Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise. Journal of Physiology. 2003.
  4. Fornaro M et al. Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells. American Journal of Physiology - Endocrinology and Metabolism. 2014.
  5. Matheny RW Jr, et al. Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010.

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