What Is IGF-1? Insulin-Like Growth Factor 1 and the GH/IGF-1 Axis Explained

What is IGF-1? Insulin-like growth factor 1 is a 70-amino-acid protein hormone that carries out much of growth hormone’s effect on growth, and it is the steadier blood marker laboratories use to read growth hormone activity. Its receptor drives two central growth-signalling pathways, and an engineered analogue of it was designed for potency in cultured cells.

This guide covers its structure, origin, binding proteins, receptor signalling, feedback and measurement, then what disorders of the axis and the cancer and lifespan research do and do not show.

What is IGF-1?

Insulin-like growth factor 1 (IGF-1) is a protein hormone made of a single chain of 70 amino acids, fixed in shape by three disulfide bonds. It belongs to a family with IGF-2 and insulin. When Rinderknecht and Humbel published its sequence in 1978, one region matched insulin’s B chain and another its A chain, and all of insulin’s cysteine positions were kept, pointing to a similar fold. The difference is processing: insulin loses its connecting C-peptide and ends up as two chains, while IGF-1 keeps a shorter, unrelated C domain plus an eight-residue D domain and stays one chain. Our guide to peptide hormones places the family in wider context.

How IGF-1 was discovered

Two research lines converged. In 1957, Salmon and Daughaday described, in their title’s words, “a hormonally controlled serum factor” that stimulated sulfate incorporation into cartilage in vitro. It grew into the somatomedin hypothesis: growth hormone controls growth through a circulating mediator, somatomedin C, thought to be made almost entirely in the liver. Separately, work on serum polypeptides with insulin-like activity led Rinderknecht and Humbel to publish the full sequences of insulin-like growth factors I and II in 1978. Somatomedin C and IGF-1 proved to be the same molecule, which is why UniProt still lists somatomedin C as an alternative name.

The GH/IGF-1 axis: where IGF-1 comes from

The hypothalamus releases growth hormone-releasing hormone (GHRH), which stimulates growth hormone (GH) secretion from the anterior pituitary, and somatostatin, which restrains it (see somatostatin, the brake on growth hormone). GH acts on the liver, which releases most blood IGF-1 and makes the main binding protein, IGFBP-3, under GH control.

The liver is not the whole story. When Sjögren and colleagues deleted the IGF-1 gene only in mouse liver cells in 1999, serum IGF-1 fell by 75%, yet postnatal growth showed no discernible change. Reviewing the evidence in 2001, Le Roith and colleagues noted that free IGF-1 stayed normal in such mice and that most tissues make IGF-1 for local (autocrine and paracrine) use; how the two pools share the work remained unresolved.

IGF-1 then closes the loop: at the pituitary it inhibits spontaneous and GHRH-stimulated GH secretion, and at the hypothalamus it suppresses GHRH expression and stimulates somatostatin. GH and IGF-1 therefore normally move together, so a mismatch is informative.

The liver’s response also varies. Insulin reaching it through the portal vein appears to set its GH sensitivity, a mechanism shown in hepatoma cells and diabetic rodents but “yet to be demonstrated in humans”. In anorexia nervosa, uncontrolled type 1 diabetes and cirrhosis, GH is high and IGF-1 low, a state of acquired hepatic GH resistance.

Compounds that act upstream

Research compounds that act on GH release sit above IGF-1. The World Anti-Doping Agency’s 2026 list classes sermorelin and CJC-1295 as GHRH analogues and GHRP-2 and GHRP-6 as growth hormone-releasing peptides, with ghrelin among the secretagogues (see what is a secretagogue?). Human evidence for the GHRPs includes short-term pharmacology: in 1990, Bowers and colleagues reported that a synthetic hexapeptide GHRP released GH in 18 normal men and acted synergistically with GHRH. That is acute hormone-release data, not evidence of longer-term effects. Our sermorelin guide, GHRP comparison and growth hormone peptides map cover the rest.

IGF binding proteins: why almost none of it is free

Six IGF binding proteins, IGFBP-1 to IGFBP-6, bind IGF-1 and IGF-2 at least as tightly as the IGF-1 receptor does, so they decide how much IGF reaches a cell. About 75–80% of serum IGF sits in a roughly 150 kDa ternary complex with IGFBP-3 (or, less often, IGFBP-5) and the acid-labile subunit (ALS); most of the rest is bound to other IGFBPs, and under 1% of IGF-1 is free. Binding sets how long IGF survives in blood: under 10 minutes unbound, about 25 minutes with one IGFBP and about 16 hours or more in the ternary complex.

Why it matters in the lab: IGF-1 LR3

Some cultured cell lines secrete their own binding proteins, which can capture added IGF-1. IGF-1 LR3, described by Francis and colleagues in 1992, adds a 13-residue N-terminal extension (the first 11 amino acids of methionyl porcine growth hormone plus Val-Asn) and swaps glutamic acid 3 for arginine, giving an 83-residue analogue. The paper’s analogues were more potent than IGF-1 in L6 myoblasts, and their gains in cell lines that secrete binding proteins were attributed to altered binding-protein interactions. See our IGF-1 LR3 research guide.

The IGF-1 receptor and its two signalling branches

The IGF-1 receptor (IGF-1R) is a receptor tyrosine kinase: a disulfide-linked tetramer whose two alpha subunits bind ligand outside the cell and whose two beta subunits carry the kinase. It binds IGF-1 with high affinity and IGF-2 and insulin more weakly, and it can pair with the insulin receptor as a hybrid. Ligand binding activates the kinase, which phosphorylates adaptors, chiefly IRS-1, IRS-2 and Shc, and two branches follow:

• PI3K–Akt–mTORC1. IRS proteins recruit PI3K; PDK1 and mTORC2 then phosphorylate Akt at Thr308 and Ser473. Akt inhibits the TSC complex, freeing Rheb to activate mTORC1 (see our mTOR explainer). This branch is linked to survival and protein synthesis.
• Ras–MAPK. GRB2 recruits SOS, which activates Ras, and Ras drives the RAF–MEK–ERK cascade (see our MAPK pathway explainer). This branch is linked to proliferation and differentiation.

Negative feedback is built in: mTORC1 or S6 kinase phosphorylates IRS proteins on serine and threonine, leading to their degradation. The insulin receptor uses the same two branches, and a 2012 review by Siddle concluded that cellular context, more than the receptors themselves, mainly explains how responses to insulin and IGF-1 differ.

How IGF-1 levels change, and how they are measured

GH levels fluctuate through the day, so IGF-1 is the steadier marker of GH activity. In a study of 15,014 people aged 0 to 94 from 12 cohorts in the United States, Canada and Europe, Bidlingmaier and colleagues found that IGF-1 falls after birth, peaks around puberty (about age 15) and declines steadily, with slightly lower averages in women.

Measurement is tricky because binding proteins must be separated first, for example under acid conditions, and any left behind can interfere. Immunoassays also differ in antibodies and calibrators. A 2012 method from Bystrom and colleagues measured intact IGF-1 by high-resolution liquid chromatography–mass spectrometry; added IGFBP-3 did not change its recovery, while two immunoassays recovered noticeably less (see our LC-MS explainer).

Results therefore need method-specific reference intervals adjusted for age and sex, ideally from assays calibrated to the international standard (02/254), as in the Bidlingmaier study. We print no ranges here: they belong to a specific method and population.

What disorders of the GH/IGF-1 axis reveal

These conditions are described here as physiology, not guidance. They are instructive because GH and IGF-1 can move together or apart.

Laron syndrome is the clearest natural experiment in IGF-1 deficiency. From 1958, Zvi Laron’s group studied short children who resembled those with GH deficiency but had very high GH; the defect lay in the GH receptor. In an Ecuadorian cohort with GH receptor mutations, Guevara-Aguirre and colleagues reported in 2011, after 22 years of monitoring, one non-lethal cancer and no diabetes among affected people, against a 17% cancer and 5% diabetes prevalence in unaffected relatives. The data are observational and concern disease, not lifespan, and they do not show that lowering IGF-1 would protect anyone else.

Mecasermin, a copy of human IGF-1, was authorized in the European Union in 2007, under exceptional circumstances, for growth failure in children and adolescents with severe primary IGF-1 deficiency. It has the native sequence; IGF-1 LR3 is a different, modified laboratory reagent.

IGF-1, cancer risk and lifespan: what the evidence supports

Cancer: consistent associations, modest sizes

IGF-1 signalling promotes proliferation and survival, so a cancer link is plausible. In a 2004 Lancet meta-regression of 21 studies with 3,609 cases, Renehan and colleagues found higher IGF-1 associated with prostate cancer (odds ratio 1.49, 75th versus 25th percentile) and premenopausal breast cancer (1.65); they called the associations modest and urged standardized laboratory methods. Mendelian randomization, which uses inherited variants as a natural experiment, tests causality more directly: in 2020, Murphy and colleagues found genetically predicted IGF-1 associated with slightly higher breast cancer risk (odds ratio 1.05 per 5 nmol/L) and judged the link probably causal. The effects are small, and none of these studies tests whether lowering IGF-1 prevents cancer; our guide to reading a peptide study explains why association and causation need different evidence.

Lifespan: striking in worms, contested in mice

In 1993, Kenyon’s group reported a C. elegans mutant that lives twice as long as wild type, and in 1997 Kimura and colleagues showed that daf-2, whose reduced signalling extends worm lifespan, encodes a member of the insulin receptor family. In mice, Holzenberger and colleagues reported in 2003 that Igf1r+/− animals lived longer, a gain later summarized as 33% in females (16% in males, not significant), and that the females resisted oxidative stress. Studying the same mutation on a different genetic background (C57BL/6) in 2011, Bokov and colleagues found a gain of under 5% in females and no significant change in males, and concluded that the mouse “is not a model of increased longevity and delayed aging”. None of this is evidence that changing IGF-1 alters human ageing.

What’s established and what isn’t

Sourcing IGF-axis research reagents in Canada

For IGF-axis work, start with the checks in our overview of research peptides in Canada, then add three specific to these molecules:

• Confirm the molecule. Native IGF-1 and IGF-1 LR3 behave differently wherever binding proteins are present, so the name, sequence and mass on the certificate should match the analogue the experiment needs.
• Ask for chromatography that separates folding variants. Mispaired disulfide isomers share the correct form’s mass, so mass spectrometry alone cannot exclude them; see our HPLC testing guide.
• Match the batch number on the certificate to the vial (see our COA guide), and ask about endotoxin testing before cell-culture work.

IGF-1 LR3The 83-residue analogue designed around binding-protein interferenceView product SermorelinA GHRH analogue, two steps upstream of IGF-1View product GHRP-2A growth hormone-releasing peptide, acting on GH releaseView product GHRP-6Classed with GHRP-2 as a growth hormone-releasing peptideView product

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