Insulin-Like Growth Factor 1 (IGF-1)

Insulin-like growth factor 1 is a single-chain peptide of 70 amino acids whose fold closely resembles proinsulin, which is where both its name and its cross-reactivity with the insulin receptor originate. Most of the circulating pool is hepatic and growth hormone-dependent, while local production in muscle, bone and cartilage acts on neighbouring cells without entering the blood. It signals through the IGF-1 receptor, a tyrosine kinase, activating the PI3K-Akt and MAPK pathways that underlie its anabolic and pro-survival effects.

Almost none of it travels free. Over 99 percent is bound, most in a ternary complex with IGFBP-3 and the acid-labile subunit too large to cross the capillary wall, extending the half-life from minutes to something like half a day. That buffering is why a single measurement is stable enough to be clinically useful, unlike growth hormone. Recombinant IGF-1 as mecasermin is approved for severe primary IGF-1 deficiency, where growth hormone is normal or high but cannot generate IGF-1.

Because it integrates growth hormone exposure over time rather than sampling a pulse, IGF-1 is the workhorse measure of the axis: the treatment target in acromegaly, a supporting test in deficiency, and a component of anti-doping biomarker panels. It is not a pure readout of growth hormone, though. Malnutrition, poorly controlled diabetes, hypothyroidism and liver disease all lower it independently of pituitary function.

The error to guard against is reading IGF-1 as a general vitality score, higher being better. Its dose-response is not monotonic in the direction wellness marketing implies: acromegaly, chronically raised IGF-1, brings arthropathy, cardiomyopathy, insulin resistance and neoplasia risk, and epidemiological work links higher IGF-1 within the normal range to modestly increased incidence of some cancers.