Month: June 2013

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GHRP2 stimulates the release of an endogeneous hormones within the somatotropes of the anterior pituitary in the animal body. Specifically, GHRP2 will increase the number of somatotropes by limiting the amount of somatostatin present while standard GHRH increases the amplitude at which the pituitary cells pulse.

Unlike ghrelin, GHRP2 is not used to increase appetite, but it may have secondary actions that will impact the hypothalamic neurons. These effects last for approximately an hour after the initial application. This mimics the natural application of GH which consists of an eight hour circulation period.

Effects on Secretions in Ovine and Rats

Previous studies investigated the actions of GHRP6 and GHRP2 on GH releases in the rat and pituitary cells, and a follow up study focused on increasing these concentrations to create GH dependency to better understand potential dosing restrictions, should this chemical be used in therapeutic sessions in the future.

• GHRP2, GHRP6 and GRF were applied in increasing concentrations to partially purified sheep somatrophs to cause a release of hormones in a dependent manner. GHRP6 was not found to increase the cAMP levels. Mixtures of GRF and GHRP2 were found to increase and cAMP levels, but a combination of GHRP2 and GHRP6 did not.

• When the cells were pretreated with an adenylyl cyclase inhibitor, they did not see a cAMP increase. This antagonist did not prevent cAMP reactions when GHRP6 was applied.

• When the antagonist was applied to the receptor, the GHRP2 and GRF combination did not increase the cAMP rates when GRF, GHRP2 or GHRP6 were applied.

These results indicate that GHRP2 can affect the ovine pituitary somatotroph to increase cAMP concentrations in a similar way that GRF does. However, GHRP2, GHRP6 or GRF all act on different receptors which would be why GHRP6 did not have an effect cAMP levels on the rat pituitary cell cultures.

Anti-Inflammatory Effects in Arthritic Rats

This study focused on the proper administration of GHRP2 on arthritic rats.

• Rats were injected with Freund’s adjuvant and then given daily exposures to GHRP2 or ghrelin fifteen days later.

• Those exposed to the ghrelin serum saw a decrease in their lepin concentrations, while those given GHRP2 saw ameliorated external symptoms of their arthritis and a decrease in their paw volume.

• GHRP2 also decreased IL-6 levels when they had originally been increased by the arthritis symptoms.

The results of this study help to show that GHRP2 may have use in managing IL-6 levels affected by arthritis. This further implies that GHRP2 may have anti-inflammatory properties as the chemical appeared to have a positive effect on managing the ghrelin receptors and immune cells that were affected by the disease.

The comparison of GHRP2 to similar chemicals in a natural setting is ongoing to assist researchers in evaluating the similarities in composition so the study of this chemical can be expanded to additional animals.

Sources:

http://joe.endocrinology-journals.org/content/148/2/197.short

http://ajpendo.physiology.org/content/288/3/E486.short

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IGF-1 des refers to the 83 amino acid IGF-1. This is a highly anabolic hormone that is typically released from the liver in animals. IGF-1 des is one of the more potent growth factors in the body of animals. It can cause muscle cell hyperlasisa as well as insulin-like reactions in the natural setting when stimulated.

Studies are currently ongoing to better determine the effects of this chemical on different tissues. This is helping researchers determine potential dosing that could someday be used to treat diseases that are associated with a lack of IGF-1 des in animal.

Effects on Brain Injuries in Adult Rats

It is known that insulin growth factors IGF binding proteins are expressed in certain regions of the brains of rats after they have experienced neuronal loss.

• It was found that three days after the hypoxic-ishemic brain injuries the IGF-2 levels would change later while central administration of the rh-IGF-1 were noticeably altered after the injury caused by neuronal loss in vivo.

• The levels of IGF-1 and IGF-2 were monitored two hours after the chemical was administered in the lateral cerebral ventricle following the injury.

• Unilateral injuries that were induced in adult rat subjects in the right carotid artery ligation was followed by a 10 minute exposure to oxygen. The neuronal loss was determined in the striatum, dentate gyrus, hippocampus and thalamus 5 days after the injury.

Administration of 20 micrograms of IGF-1 after the injury caused a reduction in neuronal loss. The trends in lowering neuronal loss remained constant until administrations of 150 micrograms of the chemical were reached. At this point there was an increase of neuronal loss in the dentate gyrus and hippocampus.

Bovine Mammary Cell Proliferation

The mammary epithelial cells were isolated in pregnant but non-lactating heifers to determine the effects of IGF-1 on these cells.

• The truncated forms of IGF-1 and IGF-2 in these cells stimulated a significant proliferation of cells.

• A media serum along with IGF-1 the mammary cells would also secret and produce an additional four species of IGF-1 binding proteins that would range from 21-48K.

• Those that were exposed to cells that were grown in a serum only saw detectable quantities of two of these major forms of the chemical at 34-48K.

Immunoblot analysis was used to identify these proteins. It was found that they were inducible if IGF was added to the serum-free media. RIA analysis was used on the bovine mammary cells to control the cultures of these secretions. Cells that were exposed to des-3 IGF-1 were 60 percent less to produce IGFBP-1 while insulin and IGF-2 failed to stimulate this production.

Ongoing studies are being applied to understand how IGF-1 des reacts in insects or amphibians as opposed to subjects like rats which fall into mammalian categories. These differences will help scientists better understand the nature of this chemical so it can be better applied for therapeutic uses in the future.

Sources:

http://endo.endojournals.org/content/137/3/893.short

http://endo.endojournals.org/content/129/2/671.short

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Click here to view or download this article in PDF format

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Igf-1 lr3 refers to the recombinant that is produced in E.Coli as non-glycosylated, single, polypeptide chain. This chemical has growth factors that comprise of an entire family of peptides, each of which are essential for growth and development in mammals.

Studies have indicated that some hormones will not directly stimulate the incorporation of sulfates into the cartilage. Instead they would act as a serum factor which is now known as somatormedin. Studies are ongoing to determine the proper levels to administer artificial versions of these chemicals to correspond with the natural activities in the body.

Effects on Protein Synthesis in the Skeletal Muscle of Rats

The actions of IGF-1 on the protein turnover rates as well as the IGF-1 receptors were monitored in the skeletal muscles of rats that suffered from sham operated pair-fed controls and chronic renal failure.

• Academia was prevented in the CRF rats while serum IGF-1 as well as skeletal muscle IGF-1 mRNA and IGF-1 was reduced in the CRF rats.

• The applications of the chemical on the studies reveal the impaired stimulation of what’s called as protein synthesis and what’s known as suppressed inhibition of the protein degradation of IGF-1 in the epitrochlearis muscles of CRF rats.

• IGF-1 has a low affinity in proteins binding IGF and the proteinase inhibitors that are obliterated by what’s been termed as the IGF-1 resistance.

Data from this study indicated that the skeletal muscle in rats with CRF has a resistance to IGF01, effect which impacts the protein synthesis and degreased IGF-1 levels. IGF-1R mRNA will increase, but the activity of the IGF-1R tyrosine kinase will be impaired– which implies that the post receptor defect can cause this resistance.

Effects of Potents on Diabetic Rats

Effects of graded applications of IGF-1 in two variants known to poorly bind with IGF proteins were examined to determine the effects of streptozotocin-induced diabetes in rats.

• The reference groups would either receive the insulin or the vehicle.

• Testing plans include marked applications to create a dependent increase in the nitrogen balance and growth rate. The highest applications of IGF-1 applied were found to increase body weight by around 48.1 g in 7 days, while the vehicle increase saw 11.0 g increases in 7 days.

• These two variants were almost 3 times more likely to restore growth than IGF-1. The group treated with insulin was more likely to gain weight but the weight that was gained was fat while those treated with the peptide gained more protein.

The application of the chemical saw an increase in muscle protein-synthesis rates and RNA levels increased by half. Insulin treatment was noted with a decrease in glucosuria and excretion. This implies that IGF-1 and its variants are capable of restoring growth in diabetic rats.

In most applications, igf-1 lr3 will exert biological activity at concentration ranges of .2-20 ng, which corresponds to the natural levels found in the body of animals. However, higher concentrations are often used during studies to better understand the effects of these chemicals on animal subjects.

Sources:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507154/

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