Growth hormone-releasing peptides are synthetic stretches of amino acids that stimulate the release of growth hormones in animal test subjects. Scientists are yet to understand their mode of operations. They have been conjectured to induce a possible dual-site of action on both our bodies’ pituitary and hypothalamus glands.

Research findings indicate that GHRPs reduce inflammation because of their antioxidant effects, thereby exhibiting cardioprotective and cytoprotective benefits. The following review highlights the similarities and differences between two hexapeptides, namely: hexarelin and ghrp-6, their mechanism of action, and effects on growth hormone release.


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 shows a high degree of similarity to GHRP-6.

The only structural difference between hexarelin and GHRP-6 is the inclusion of two methyl groups in the structure of GHRP-6. This peptide remains active both orally and sublingually and displays high selectivity in its mode of action. It has been extensively studied because of its impact on cardiac cell survival after ischemia and nutrient deprivation.

However, it has higher stability and more biological effect 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 binds to specific receptors at both the pituitary and hypothalamic levels to induce hormone release in animal test subjects through phospholipid-dependent protein kinase (PKC) signaling. It mimics the action of ghrelin by binding to the growth hormone secretagogue receptor 1a (GHS-R1a) and also interacts with and activates the cardiac receptors CD36.


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 studied in animal model studies and was identified more than a decade ago.

GHRP-6 recognizes and binds to specific receptors present at the pituitary or hypothalamic level. Studies showed that GHRP-6 receptors are also 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.


Studies in animal test subjects show that GHRP-6 stimulates ghrelin which increases the production of growth hormone (GH) by acting at the level of the pituitary or hypothalamus through a specific receptor different from that of the endogenous Growth Hormone-Releasing Hormone (GHRH).

The four important parts of the test subjects that demonstrate the role of GHRP-6 include the pituitary gland, central nervous system, liver, and stomach.

1. Protects the Heart
Research on murine models has shown that hexamorelin protects cardiac cells from injury in the backdrop of cardiac arrest. It interacts with CD36 receptors and prevents apoptosis of the cardiac cells. The peptide helps improve 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 to improve cardiac function by altering the processing of calcium and potassium by cardiac muscle cells.
Interestingly, the study also proves GHRP-6 to be partially superior in function as compared to ghrelin.

GHRP-6 mediates cardiac remodeling by switching the nervous system response from sympathetic (includes increased blood pressure, heart rate, etc.) to parasympathetic. This regulation helps to improve short-term health and outcomes, in addition to reducing the need for prolonged cardiac medication as well as scar tissue healing.

2. Protects muscle
The peptide has been observed to protect muscle cells in general and is not useful specifically for the heart alone. GHRP-6 controls calcium flow and mitochondrial dysfunction in muscles of rats suffering from cachexia (extreme weight loss due to illness or chemotherapy). It also helps to keep muscle cells viable by maintaining mitochondrial integrity. Thus, GHRP-6 may help reestablish proper calcium regulation post-chemotherapy as calcium ion levels get disturbed.

3. Improves Fat Measures
Dyslipidemia is the physiological condition of elevated fat levels in the blood. GHRP-6 helps to reduce blood sugar and insulin resistance in rats. It can therefore be used as an alternative to the existing lipid medications to treat severe dyslipidemia.


Both peptides have a similar influence as seen in animal research with few variations. They both cause weight loss, lean muscle growth, cardioprotection, improved recovery from injuries, etc.

However, hexarelin is rated better than GHRP-6 because it easily stimulates GH, ACTH (adrenocorticotropic hormone), cortisol, and prolactin even during sleep. But plasma glucose, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and insulin-like growth factor-1 are not affected by hexarelin administration. It also doesn’t enhance ghrelin like GHRP-6 and has a longer half-life.



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