Insulin-like growth factor 1 (IGF-1)
Also known as: IGF-1, somatomedin C
A 70-amino-acid peptide made mainly by the liver under GH stimulation that mediates the growth-promoting effects of GH and provides negative feedback on the GH axis.
Overview
IGF-1 is structurally related to proinsulin. GH stimulates its synthesis in hepatocytes (the source of most circulating IGF-1) and in many target tissues, where it acts locally. In plasma, ≈75 % is held in a ternary complex with IGFBP-3 and the acid-labile subunit, giving a long half-life (≈12–15 h) and stable levels — unlike pulsatile GH. Free IGF-1 binds the IGF-1 receptor, a receptor tyrosine kinase closely related to the insulin receptor, activating the PI3K–Akt and MAPK pathways to drive cell proliferation, differentiation and survival.
At the growth plate, IGF-1 stimulates proliferation and hypertrophy of chondrocytes; it also promotes muscle and bone growth. At high concentrations it can bind the insulin receptor and cause hypoglycaemia (some large tumours secrete the related IGF-2 and cause non-islet-cell tumour hypoglycaemia). IGF-1 inhibits GH secretion directly at somatotrophs and by stimulating hypothalamic somatostatin.
- Location
Source: liver (endocrine), plus chondrocytes, bone, muscle (paracrine/autocrine). Targets: almost all tissues, especially growth-plate chondrocytes, muscle and bone.
Function
- Mediates GH-dependent linear growth and anabolism.
- Provides negative feedback on GH secretion.
- Promotes cell survival and proliferation.
- Physiology
Class: peptide (70 aa). Receptor: IGF-1R — receptor tyrosine kinase. Half-life ≈12–15 h when bound to IGFBP-3/ALS.
- Regulation
Increased by GH, insulin and adequate nutrition; reduced by malnutrition, liver disease, hypothyroidism and GH deficiency or resistance. Levels peak in puberty and fall with age.
Clinical significance
Screening test for acromegaly
Because IGF-1 integrates GH secretion over 24 h, an age- and sex-matched raised IGF-1 is the best screening test for acromegaly and the main marker of treatment response.
Test yourself
Which test best confirms suspected acromegaly?
- Random serum GH
- Failure of GH to suppress during a 75 g oral glucose tolerance test, with raised IGF-1
- Short Synacthen test
- Overnight dexamethasone suppression
Answer: Failure of GH to suppress during a 75 g oral glucose tolerance test, with raised IGF-1
GH is pulsatile, so random levels mislead. Glucose normally suppresses GH; failure to suppress, together with a raised IGF-1 (stable integrated marker), confirms autonomous GH secretion.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.