insulin-like growth factor
Summary
Insulin-like growth factor 1 (IGF-1) is a peptide hormone produced mainly by the liver in response to growth hormone (GH) stimulation. It mediates most of GH's anabolic and growth-promoting effects on bone, cartilage, and muscle. IGF-1 levels are used clinically as a stable marker of GH activity, useful in diagnosing GH excess (acromegaly) or deficiency.
Detail
IGF-1 (somatomedin C) is part of the GH/IGF-1 axis: hypothalamic GHRH stimulates anterior pituitary somatotrophs to release GH, which acts on the liver (and other tissues) to produce IGF-1. IGF-1 then exerts negative feedback on both GHRH and GH secretion, and also stimulates somatostatin release. Structurally, IGF-1 is homologous to proinsulin and can bind (with lower affinity) to insulin receptors, explaining its mild hypoglycemic activity and the phenomenon of 'insulin-like' effects.
Physiologic actions: IGF-1 promotes chondrocyte proliferation at the epiphyseal growth plate (linear bone growth), stimulates protein synthesis and cellular hypertrophy/hyperplasia in muscle, and has mitogenic and anti-apoptotic effects in many tissues. It works in both endocrine (liver-derived, circulating) and autocrine/paracrine (locally produced in various tissues, especially growth plates) fashion.
Clinical relevance: - Acromegaly/Gigantism: Excess GH (often from pituitary adenoma) leads to elevated IGF-1, causing bone overgrowth, soft tissue enlargement, organomegaly, insulin resistance, and increased cancer risk (e.g., colon polyps). IGF-1 is the preferred screening test since it reflects average GH secretion (GH is pulsatile). - GH deficiency: Low IGF-1 causes growth failure/dwarfism in children; diagnosed with GH stimulation tests along with low IGF-1. - Laron syndrome: GH receptor defect causing GH resistance; high GH but low IGF-1, since the liver cannot respond to GH. - Diabetes and cancer: IGF-1 signaling is implicated in tumor growth (e.g., breast, prostate, colon cancer) due to its proliferative and anti-apoptotic effects; recombinant IGF-1 (mecasermin) is used to treat some growth disorders. - Pharmacology: Octreotide (somatostatin analog) is used to suppress GH/IGF-1 in acromegaly; pegvisomant (GH receptor antagonist) directly blocks IGF-1 production.
Key associations for boards: IGF-1 is a downstream mediator of GH; used to screen for acromegaly (elevated levels, confirmed by oral glucose suppression test failing to suppress GH); IGF-1 receptor structurally resembles insulin receptor (tyrosine kinase activity); IGF-1 is central to the somatomedin hypothesis of growth regulation.
Sources
- First Aid for the USMLE Step 1
- Guyton and Hall Textbook of Medical Physiology
- Harrison's Principles of Internal Medicine
- Robbins Basic Pathology
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