Growth hormone-releasing peptides are synthetically developed stretches of amino acids that are considered to act as potential stimulators in the release of growth hormones in animal research models, though scientists have yet to elucidate their exact mechanism of action. They have been conjectured to induce a possible dual-site of action on both the pituitary and hypothalamus glands.
Research findings indicate that GHRPs may possibly reduce inflammation due to their potential antioxidant activity, which may exert cardioprotective and cytoprotective impacts. The following review highlights the similarities and differences between hexapeptides Hexarelin and GHRP-6, what contemporary research suggests are their mechanisms of action, and their proposed impact on the natural production and release of endogenous growth hormone.
Hexarelin Peptide Overview
Hexarelin is a new synthetic growth hormone-releasing peptide (GHRP), a synthetic analog of ghrelin (a 28 amino acid peptide), and closely related to GHRP-6. It is a synthetic analog of ghrelin and researchers indicate it exhibits a high degree of similarity to GHRP-6.
The only structural difference between Hexarelin peptide and GHRP-6 is the inclusion of two methyl groups in the structure of GHRP-6. It has been extensively studied within the context of cardiac cell survival after ischemia and nutrient deprivation. However, it is considered to exhibit higher stability and potentially more biological impact than ghrelin. It is a six amino acid peptide with the sequence (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2). It has an empirical formula of C47H58N12O6 and has a molecular weight of 887 g/mol.
Hexarelin peptide has been proposed to act as a binding agent to specific receptors at both the pituitary and hypothalamic levels to potentially induce hormone release in animal research models through phospholipid-dependent protein kinase (PKC) signaling. It appears to mimic the action of ghrelin through apparent binding to the growth hormone secretagogue receptor 1a (GHS-R1a) and may also interact with and activate the cardiac receptors CD36.
GHRP-6 Overview
Growth hormone-releasing peptide-6 is a first-line synthetic hexapeptide and a met-enkephalin derivative. It comprises a chain of 6 unnatural D amino acids with the sequence (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2). It happens to be the first hexapeptide of its class employed in animal research studies, despite being identified more than a decade ago.
GHRP-6 has been posited by researchers to recognize and binds to specific receptors present at the pituitary or hypothalamic level. Studies suggest that GHRP-6 receptors may also be prevalent in peripheral tissues such as the heart, adrenal, ovary, testis, lung, and skeletal muscle. The empirical formula of the peptide is C46H56N12O6, and it has a molecular weight of 873 g/mol.
Hexarelin Peptide and GHRP-6 Proposed Mechanism of Action
Studies using animal research models suggest that GHRP-6 may stimulate ghrelin to increase the production of growth hormone (GH) at the level of the pituitary or hypothalamus, acting through a specific receptor different from that of the endogenous Growth Hormone-Releasing Hormone (GHRH). The four vital areas of concentrated observation in these studies include the pituitary gland, central nervous system, liver, and stomach of the research models.
1. Heart Cells
Research on murine models has suggested that Hexamorelin may exert protective impact on cardiac cells from injury in the context of cardiac arrest. The peptide appeared to interact with CD36 receptors, thereby possibly preventing apoptosis of the cardiac cells. The peptide may support cardiac function, increasing the number of surviving cardiac cells and reducing the levels of malondialdehyde (cardiac cell death marker). Studies in rat models of diabetes have also observed Hexarelin peptide to potentially impact cardiac function by altering the processing of calcium and potassium by cardiac muscle cells. Interestingly, the study also suggested GHRP-6 may potentially be partially superior in function when compared to ghrelin.
GHRP-6 appears to mediate cardiac remodeling by switching the nervous system response from sympathetic (includes increased blood pressure, heart rate, etc.) to parasympathetic, which may positively impact short-term function following dysfunction or irregularity.
2. Muscle Cells
Researchers suggest the peptide may act to protect muscle cells. GHRP-6 appears to influence some control in calcium flow and mitochondrial dysfunction in the muscles of rat models of cachexia. The study findings also indicate that the peptide displays some potential to maintain muscle cell viability through maintaining mitochondrial integrity. GHRP-6 may potentially help reestablish proper calcium regulation following any disturbing of calcium ion levels.
3. Fat Cells
Dyslipidemia is the physiological condition of elevated fat levels in the blood. GHRP-6 has been hypothesized by researchers to potentially reduce blood sugar and insulin resistance in rat models. It may follow the same mechanism of action as traditional lipid compounds within the context of severe dyslipidemia.
Hexarelin Peptide and GHRP-6: A Comparison
Both peptides appear to exert a similar influence as seen in animal research with few variations. They both have been researched within the context of weight loss, development and proliferation of muscle cells, and have ben affiliated with cardioprotection and improved tissue repair processes.
Hexarelin peptide has a more supportive body of research behind it than GHRP-6, with studies generally indicating that the compound may more easily stimulate growth hormone production, ACTH (adrenocorticotropic hormone), cortisol, and prolactin, even during sleep cycles. But plasma glucose, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and insulin-like growth factor-1 are examples of hormonse that have so far not been found to be affected by Hexarelin peptide exposure. It does not appear to enhance ghrelin, in the way GHRP-6 has been hypothesized to, and is considered to have a longer half-life.
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