GHRP-6: The first effective growth hormone secretagogue

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GHRP-6 is a growth hormone secretagogue that has been found to enhance tissue viability in various organs. The systemic administration of GHRP-6 (which is an agonist for the ghrelin receptor) has been shown in research to increases insulin-like growth factor (IGF-1) levels in various brain regions, including the hypothalamus, but GHRP-6's effects are much broader than just the area of the brain and why I wish to dive deep into the positive traits that has already been seen in GHRP-6 research.


GHRP-6 was the first of a family of synthetic peptides discovered that will enhance the release of the Growth Hormone by the pituitary gland in a dose-dependent manner and as a chain reaction also cause a rise in IGF-1 levels in the body. GHRP-6 is one of a few synthetic analogs that include unnatural D-amino acids that were developed for their growth hormone releasing activity. Growth Hormone and IGF-1 play a big role in cell formation and energy metabolism in the body, amongst other things and since its discovery it has been used as a starting point for a vast amount research that was aimed to obtain new compounds and treatments out of it.


GHRP-6 acts as a synthetic ghrelinmimetic in the Growth Hormones secretagogue receptor better now knows as the "receptor's natural endogenous ligand" and through its action there Growth Hormone is released into the body. Ghrelin was first identified during research in the rat stomach as an endogenous ligand for the growth hormone secretagogue (GHS) and GHRP-6 was invented after these early findings. Ghrelin is a "hunger" peptide hormone that is responsible for not just the feeling of hunger in animals but also various other affects in the body such as growth and regulating energy balance. Ghrelin has since then been found to be a very potent stimulator of growth hormone from the anterior pituitary gland. Ghrelin has also been found to protect the cardiovascular system after cardiopulmonary bypass (CPB). It has been found to significantly increase cardiac function after CPB and in cultured cardiomyocytes that were subjected to simulated CPB. It was found that ghrelin increased cell viability, decreased the amount of apoptotic myocytes and may even contribute to the inhibition of inflammatory response through the Akt-activated pathway.
It has also been noted in research that the inhibition of ghrelin blocked its cardioprotective effects in both vivo and vitro research studies. Understanding a little bit about Ghrelin matters because GHRP-6 is closely related to Ghrelin being that GHRP-6 is also a GHS and has been found to have many of the same positive traits. What differs between Ghrelin and GHRP-6 is that GHRP-6 is a man-made peptide and it has been very effective in furthering research in the field of GHS's and seeing the many possible beneficial applications they may have for better understanding and developing treatments for some serious conditions such as; MS, diabetes, organ failure and wasting disease, just to name a few.


The systemic administration of GHRP-6 has been deemed by many researchers to be a very effective agonist for the ghrelin receptor and has been shown in research to increases insulin-like growth factor (IGF-1) levels in various brain regions, including the hypothalamus. Keep in mind that GHRP-6's effects are much broader than just the area of the brain. Growth hormone plays a large role in just about every living animal. From tissue regeneration to new cell formation, it is a very important compound to any growing species. By better understanding GHRP-6's actions in the body it may be possible to get a better understanding of how its administration may help some illnesses and possibly come up with better treatments or even preventative actions for them.


Below is a list of what I feel are some of the more important findings in current research with GHRP-6:


1) Neuroprotective effects


There has been many recent studies showing various positive results with GHRP-6 research and in a recent study with GHRP-6 it was demonstrated for the first time that GHRP-6 has a neuroprotective effect in the caspase-independent cell death pathway and that GHRP-6 has a neuroprotective effect independent of its action on GH or IGF-1 levels in the body. I think that is pretty amazing that this compound would have action on its own like this aside from its effects on Growth Hormone. GHRP-6 did this by partially reversing glutamate-induced cell death but not the activation of caspases and what this suggests is a blockage of the caspase-independent cell death pathway with GHRP-6 administration.

2) Effects on diabetes


GHRP-6 administration showed an increased glucose transporter-4 gene expression and potentiated insulin's effect on epididymal fat mass, adipocyte size and glucose transport. It was also shown that GHRP-6 and insulin exert an additive effect on weight gain and visceral fat mass accumulation in diabetic rats that some of GHRP-6's metabolic effects depend on the insulin/glucose status in the body during administration. This is of great importance to researchers because poorly controlled type1 diabetes has been associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. This is very important because although insulin administration can delay diabetic complications, it will not prevent them. Ghrelin and GHS?s like GHRP-6 have been shown to prevent apoptosis in different tissues and to modulate glucose homeostasis, so I believe a combined peptide treatment may be beneficial to subjects with diabetes over just insulin administration alone. In a recent rat study it was found that "only the combined treatment of insulin + GHRP-6 decreased diabetes-induced apoptosis. In conclusion, insulin and GHRP-6 exert tissue specific effects in STZ-diabetic rats and act synergistically on some processes." Further research in this area is a must since it has been shown that insulin administration alone is not effective in preventing some of the diabetes-induced alterations that may happen in the central nervous system of test subjects.


3) Effects of GHRP-6 in ovariectomized subjects


There has been research with combining hormones and GHRP-6 administration and that has shown more promising results verses hormone administration alone. In a study geared towards assessing the effect of both estrogen and GHRP-6 on cardiovascular and metabolic diseases commonly seen in in ovariectomized rats; it was shown that administration of this compound to the ovariectomized rats failed to produce significant change in both the body weight gain and food intake. The GHRP-6 administration in this study did revers the effect of the ovariectomized subjects fasting serum glucose, insulin, insulin resistance and lipid fractions and this is important because the decrease in ovarian hormones produced by ovariectomized subjects results in a rise of several risk factors related to carbohydrate metabolism and the cardiovascular system. This study also showed that the effect of GHRP-6 on improving dyslipidemia after a subject was ovariectomized was more potent than that of estrogen, which is very interesting. This research shows that these negative effects can be reversed by GHRP-6 administration and I feel that the co-administration of estrogen and GHRP-6 may be the future protocol over estrogen administration alone under these circumstances.


4) GHRP-6 and Multiple sclerosis


Multiple sclerosis (MS) is a very complex and potentially devastating autoimmune disease which mainly affects the central nervous system. Researchers looked into the effects of GHRP-6 in test subjects with MS and what they found was that administration of GHRP-6 reduced the negative effects in subjects with mild to severe cases of MS. It was found that GHRP-6 administration also improved the survival rate in nearly 100% of the test subjects. Possibly in part by the increase in the brain IGF-1 transcript and a decrease of serum MDA which was found in subjects administered GHRP-6 in this study. GHRP-6 was also found in similar research to be a suitable therapeutic approach for the acute management of stroke. These are very important findings because up until recently a wide variety of drugs have been evaluated in MS and stroke research, with little success. The research into GHRP6 and MS may be the stepping stone to better understanding this horrible condition and finding effective ways to treat or prevent it.


5) Effects on organ failure


An area of research that I feel is lacking in effective treatment protocols is the area of multiple organ failure (MOF). Thankfully researchers are already looking into this with GHRP-6 and in a very recent study researchers examined the effect GHRP-6 on cell migration and proliferation using an intestinal epithelial along with colonic cancer (HT29) cells. What they found was that administration of GHRP-6 (120 microg/kg of body weight) may provide a new and simple approach for the prevention and treatment of MOF along with other injuries of the gastrointestinal tract. In this same study it was found that GHRP-6, also, reduced lung and renal injuries in the test subjects.


6) Effects on the heart


There are various strategies currently used at enhancing survival after myocardial injury (heart attack) but I feel many are not optimal and I feel we can do better. In a recent study with GHRP-6; researchers looked into the effects of GHRP-6 administration following myocardial injury to see if there were any positive effects. More specifically the aim for the research was to see if GHRP-6 administration would reduce myocardial infarct size following an acute coronary occlusion in vivo. What they found was that the levels of oxidative stress markers suggested that this peptide prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems, yet, myocardial IGF-1 transcription was not found to be amplified by GHRP-6. What this suggests to me is that this peptide has an antioxidant effect which may partially contribute to reduce myocardial ischaemic damage and other researchers are coming to the same conclusion.


This amazing peptide is one of those novel compounds that just seem to hit the ground running and I am really happy many researchers are now exploring its many possible applications in their research. I truly hope that this glimpse at what GHRP-6 has already been found to do will excite more researchers to explore this peptide further and find new understandings and ways to use this very amazing compound for their research purposes.




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Ref:


1) Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response Cardioprotective effect of ghrelin in cardiopulmona... [PLoS One. 2013] - PubMed - NCBI
2) Protective effect of GHRP-6 and estrogen supplementation against some cardiometabolic risk factors in ovariectomized rats Protective effect of GHRP-6 and estrogen supple... [Endocr Regul. 2012] - PubMed - NCBI
3) Epidermal growth factor and growth hormone-releasing peptide-6: combined therapeutic approach in experimental stroke Epidermal growth factor and growth ho... [Restor Neurol Neurosci. 2013] - PubMed - NCBI
4) Coadministration of epidermal growth factor and growth hormone releasing peptide-6 improves clinical recovery in experimental autoimmune encephalitis Coadministration of epidermal growth ... [Restor Neurol Neurosci. 2011] - PubMed - NCBI
5) Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary Insulin and growth hormone-releasing pep... [Mol Cell Endocrinol. 2011] - PubMed - NCBI
6) The positive effects of growth hormone-releasing peptide-6 on weight gain and fat mass accrual depend on the insulin/glucose status The positive effects of growth hormone-releasi... [Endocrinology. 2010] - PubMed - NCBI
7) Effects of ghrelin, growth hormone-releasing peptide-6 in type 1 diabetes mellitus Effects of ghrelin, growth hormone-releasing pept... [Metabolism. 2010] - PubMed - NCBI
8) Growth hormone-releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin-like growth factor I Growth hormone-releasing peptide 6 protection... [Eur J Neurosci. 2009] - PubMed - NCBI
9) Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction Growth-hormone-releasing peptide 6 (GHRP6) p... [Clin Sci (Lond). 2007] - PubMed - NCBI
10) Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failurehttp://www.ncbi.nlm.nih.gov/pubmed/16417467
11) Growth hormone-releasing peptide-6 increases insulin-like growth factor-I mRNA levels and activates Akt in RCA-6 cells as a model of neuropeptide Y neurones Growth hormone-releasing peptide-6 increas... [J Neuroendocrinol. 2005] - PubMed - NCBI




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