标签： LDH

Somatomedin C, IGF-I, IGFI, IGF1, IGF-IA MGF.

The somatomedins, IGFs, comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of GH. Early studies showed that GH did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed ‘sulfation factor,’ which later became known as ‘somatomedin. Three main somatomedins have been characterized: somatomedin C , somatomedin A , and somatomedin B.

IGF1 Human Recombinant produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 70 amino acids and having a molecular mass of 7.6kDa.
IGF-1 is purified by proprietary chromatographic techniques.

The protein was lyophilized from a concentrated solution in PBS, pH 7.0.

Lyophilized IGF1 although stable at room temperature for 3 weeks, should be stored desiccated below -18°C. Upon reconstitution IGF1 should be stored at 4°C between 2-7 days and for future use below -18°C.
For long term storage it is recommended to add a carrier protein .
Please prevent freeze-thaw cycles.

Greater than 97.0% as determined by:
Analysis by RP-HPLC.
Analysis by -PAGE.

The biological activity was determined by the cell proliferation assay using serum free human MCF-7 cells in <2ng/ml, corresponding to a Specific Activity of >5.0 x 10⁵IU/mg.

IGF stands for INS like growth factors, which are proteins that have a high similarity to INS. They are part of a complicated process that uses cells to communication with the physiologic environment around them. IGF’s complex system is often called the ‘axis’. This consists of:
● Two cell-surface receptors
● Two ligands
● A family of six high-affinity IGF-binding proteins.
● Proteases.

The Effect IGF Has On The Body
Many unique tissue types express the IGF-1 receptor, and the effects can vary. It induces the survival of neurons, may catalyse skeletal muscle hypertrophy by inducing protein synthesis, and by blocking muscle atrophy. It works as a protector for cartilage cells, and may work to be an anabolic factor for the bones. When used in high concentrations, it can activate the INS receptor, and can even complement the effects that INS has on the body.

Diseases And IGF
Diseases and IGF are closely related, and a number of them can be affected. The INS IGF axis is thought to have an effect on aging, with an increased life span shown in fruit flies when used in studies.
It is also important to note the crucial role that IGF plays in cancer and diabetes – IGF- 1 has been shown to stimulate growth in both prostate and breast cancer cells. The degree of risk that IGF-1 poses is up for debate, and many scientists are not in agreement. IGF has also shown to have the ability to decrease blood glucose levels, although not quite as effective as INS.

How Was IGF Discovered?
Investigators began studying the effects of biological substances on cells and tissues outside the body when IGFs were discovered. The name is self explanatory in the fact that IGF performs INS actions in some tissues, but is less potent than INS at decreasing blood sugar. Its fundamental action is to stimulate growth, whether that be within the epidermal growth factor or the nerve growth factor.

What’s The Difference Between IGF-1 And IGF-2?
The two types of IGF are IGF-1 and IGF-2. Although the names are similar, the specific actions that they take are different – they bind and activate completely difference receptors. The major actor in them both is the effect that they have on cell growth. Most of the actions of the pituitary GH are mediated by IGFs, but predominantly IGF-1. GH works to stimulate many tissues within the body, especially the liver which then secretes IGF-1. This then causes hypertrophy, or in layman’s terms, an increase in cell size, as well as hyperplasia which is an increase in the number of cells.
The IGF-1 concentration will increase during childhood and hit peak during puberty, but will then decrease afterwards, as does the hormone secretion itself. It has been proven that children and adults with a deficiency of the GH have low serum IGF-1 concentrations when put in comparison with others in the same age range. Patients who have conditions like acromegaly have been shown to have increased serum IGF-1 concentrations. The production of IGF-2 is less dependent on the secretion of GH than IGF-1, and is much less important for stimulating linear growth.

Also referred to as Somatomedin C, the IGF1 protein is encoded in humans as the IGF1 gene. Molecularly, IGF-1 does share similarities with INS and has a number of important roles in the body. For instance, it is a main part of childhood growth and during the later stages of adult life, creates anabolic impacts.

Structure
Made up of three helical segments, these IGF-1 structures are connected by the C-region. This is a 12-residue linker. Studies have shown that the dynamic structure of this protein is similar to INS however there is very little evidence of structural definition in the C-region. The C-region has been shown through studies to extend away from the IGF-1 core and has residues that are involved with receptor binding.

Function
Studies have shown that IGF1 does cause the somatic growth in fetal mammals. Somatic growth in postnatal animals is also achieved through interactions with the GH and IGF-1. If IGF-1 is overexpressed, then it causes the malignant change of cultured cells. Increased levels of IGF-1 have been seen in a variety of tumors in the human body. Furthermore, other research has shown that down regulations of IGF-1 protein can actually reverse the impact on tumor cells. Indeed, it could even make these cells sensitive to programmed cell death. Investigations into this type of function has lead to IGF-1 being targeted as a key possibility for developing anti tumor agents.
Clinically, there are various diseases that are characterized by an inability to either respond to or create IGF-1. An example of this would be Laron dwarfism. In this case, treatment using a GH is not effective due to the fact that there is a lack of GH receptors present in the body. Patients suffering from this condition will typically have IGF-1 levels below three SD. Interestingly, people suffering from these conditions are less likely to develop conditions such as diabetes and cancer.

Mechanism
IGF-1 functions mainly as a mediator for the impact of GH. This hormone is made in the anterior pituitary gland. Once created it is released into the bloodstream. Eventually it reaches the liver where it triggers the production of IGF-1.
IGF-1 causes growth-promotion in virtually every part of the body including cells in the lungs, skin, bone, kidney liver and many more as well as providing, INS-like effects. Beyond replicated the impact of INS on the body, the protein is also capable of regulating cellular DNA synthesis.

Interactions
IGF-1 interact with each of the seven IGF-1 binding proteins or IGFBPs. This includes IGFB1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6 and IGFBP7. However, it’s important to be aware that some are inhibitory. Two examples of this would be IGFBP-5 and IGFBP-2. Both will bind IGF-1 at an affinity higher than it binds its own receptor. As such, serum levels of these two will actually lower the activity of IGF-1.
Research is constantly ongoing into the function and impact of IGF-1 on the processes in the human body and it’s possible use to treat diseases like cancer.