What Are Somatomedins and Where Are They Synthesized?
Somatomedins (insulin-like growth factors, IGF) are biologically active molecules. Their primary site of production is the liver.
Two main types are distinguished:
- Somatomedin C (IGF-1).
- Somatomedin A (IGF-2).
Growth hormone (GH), secreted by the anterior pituitary gland, stimulates the production of somatomedins in the liver.
Mechanism of Action and Physiological Effects
Somatomedins are the primary mediators of the anabolic actions of growth hormone.
- Tissue Growth: The GH and IGF-1 axis stimulates bone tissue growth, which is especially important during adolescence. During the embryonic period, this function is predominantly mediated by IGF-2.
- Anabolism and Proliferation: Somatomedins exert a direct stimulating effect on cell proliferation and amino acid anabolism.
- Effect on Mesenchyme: Insulin-like growth factors stimulate the proliferation of cells of mesenchymal origin, participating in tissue growth and stroma formation.
How Is Production Regulated (Regulatory Axis)?
The synthesis of somatomedins is regulated by the hypothalamo-pituitary axis:
- The hypothalamus releases growth hormone-releasing hormone (GHRH).
- Via the hypophyseal portal system, GHRH reaches the adenohypophysis and stimulates the production of growth hormone (GH).
- GH stimulates the liver to produce IGF-1.
Role in Pathology and Clinical Significance
- Tumor Growth: Stromal fibroblasts in lung cancer can produce IGF-2. Via a paracrine mechanism, it binds to receptors on cancer cells and stimulates their proliferation.
- Benign Breast Disease: Elevated levels of IGF-1 are positively associated with the risk of breast cancer development.
- Liver Fibrosis: IGF-1 is among the growth factors involved in stimulating hepatic fibrogenesis. Fibrosis is associated with the replacement of dead hepatocytes with connective tissue and an imbalance between extracellular matrix synthesis and degradation.
- Liver Cirrhosis and Sarcopenia: In patients with decompensated liver cirrhosis, hyperammonemia, and sarcopenia, combination therapy with ornithine leads to a decrease in IGF-1 levels. This is viewed as a potential mechanism for correcting sarcopenia; ornithine positively impacts muscle function, mass, and strength.