The liver produces them predominantly when the growth hormones act on the target tissue.
Somatomedins inhibit the release of growth hormones by acting directly on the anterior pituitary gland and by stimulating somatostatin secretion from the hypothalamus.
Somatomedins are a group of proteins that promote growth and cell division in response to stimulation by growth hormone (GH), also known as somatotropin (STH).
Somatomedins have biological effects similar to somatotropin.
In addition to their actions that stimulate growth, somatomedins also stimulate the production of somatostatin, which suppresses the release of growth hormones.
Therefore, somatomedin levels are controlled by negative feedback through somatostatin and growth hormone intermediates.
Somatomedins are produced in many tissues and have autocrine, paracrine, and endocrine actions. It is believed that the liver is the predominant source of circulating somatomedins.
Three forms include:
- Somatomedin A is another name for the growth factor similar to insulin 2 (IGF-2).
- Somatomedin B is derived from vitronectin.
- Somatomedin C is another name for the growth factor identical to insulin 1 (IGF-1).
Historical background of Somatomedina
IGFs (somatomedins) are a family of peptides that partly depend on growth hormone and mediate many of the anabolic and mitogenic actions of growth hormone.
They were initially identified in 1957 for their ability to stimulate [35 S] -sulfate incorporation in rat cartilage and were termed sulfation factors.
In 1972, that term was replaced by somatomedin, and the purification of somatomedin from human serum produced a basic peptide (somatomedin C) and a neutral peptide (somatomedin A).
In 1978, Rinderknecht and Humbel isolated two active somatomedins from human plasma and, after demonstrating a striking structural resemblance to proinsulin, renamed them insulin-like growth factors (IGF).
Growth factors similar to insulin
Insulin-like growth factor I (IGF-I) is a 70 amino acid polypeptide and is one of several insulin-like growth-related factors present in the circulation.
The molecule shows approximately 50% sequence homology with proinsulin and has a series of biological activities similar to insulin.
The peptide is growth hormone (GH), which depends heavily, but there is increasing evidence of growth hormone-independent secretion. IGF-I has considerable growth-promoting effects, including mitogenic effects and the promotion of cartilage sulfation.
It also intervenes in the actions to promote growth hormone growth in skeletons and other body fluids. Almost all (> 95%) of serum IGF-I circulates bound to specific growth factor binding proteins, of which six classes are now recognized (IGF-BPs 1-6).
It is believed that BP3 is the main IGF-I binding protein, forming a ternary complex of 140,000 daltons with IGF-I and an acid-labile subunit. The measurement of IGF-I in serum is of recognized value in children with growth disorders and the diagnosis and monitoring of acromegaly.
For the diagnosis of acromegaly, a single determination of IGF-I is considered more reliable than a random determination of the growth hormone.
Somatomedin-C (SM-C), or insulin-like growth factor I (IGF-I), is a simple 70-amino acid basic chain polypeptide similar to proinsulin (50% sequence homology) and the other member Well-characterized of the somatomedin family: IGF II (67AA, 70% sequence homology with IGF-I).
Somatomedin-C is the most critical factor which mediates the growth promotion actions of growth hormone, a pituitary hormone with highly fluctuating blood levels due to pulsatile release.
The blood concentration of Somatomedin-C is more stable due to binding to carrier proteins.
The concentration of the predominant binding protein and the production of Somatomedin-C is regulated by growth hormone. Somatomedin-C is produced by the liver and other tissues and has endocrine, paracrine, and autocrine activities.
Stimulates growth and regulates the differentiation of various tissues, shows activities similar to insulin, and promotes cartilage growth.
Although growth hormone is the most critical factor controlling the secretion and concentration of Somatomedin-C, other factors are also determinants: age (with a peak in adolescence), sex, nutritional status, and other hormones (estrogen, thyroxine, prolactin).
The specific trophic stimuli mainly control the secretion of Somatomedin-C in the local microenvironment of a particular organ (paracrine activities). At the same time, the concentration of Somatomedin-C in the blood is the most crucial variable for balanced systemic growth (endocrine activities).
Studies of IGF-1
Somatomedins, or insulin-like growth factors (IGF), comprise a family of peptides that play an essential role in the growth and development of mammals. IGF-1 mediates many of the effects of promoting growth hormone growth.
Diabetes leads to decreased liver production of IGF-1, and a subsequent decrease in serum IGF-1 leads to an excess in growth hormone secretion. The increase in growth hormone can, in turn, stimulate local IGF1 pathways in other tissues (i.e., the kidney).
It has been shown that IGF-1 in vitro increases the proliferation of mesangial cells. Mesangial cells from non-obese diabetic mice (NOD) secrete an increase in IGF-1, and it is believed that the consequent reduction in MMP-2 activity leads to an accumulation of specialized extracellular glomerular matrix.
The increase in renal IGF-1 could be caused by changes in the renal receptors of IGF-1 and IGF-1 binding proteins rather than an increase in the local production of IGF-1 in the kidney.