Hexarelin is a synthetic growth hormone-releasing peptide which activates the growth hormone secretagogue receptor (GHSR) in the brain; this is the action that mimics the natural hormone ghrelin. But, once the peptide makes it to the bloodstream, its action goes beyond hormone release.
Hexarelin is highly valued among the researchers since it’s chemically more stable and functionally more potent than ghrelin.
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Hexarelin is a growth hormone-releasing peptide (GHRP) that researchers believe may exhibit similar activity to peptide GHRP-6. Also known as Examorelin, Hexarelin is a synthetic peptide made up of six amino acids. In terms of its mechanism of action, Hexarelin is believed to behave like ghrelin, a naturally occurring peptide made up of 28 amino acids, which stimulates the release of growth hormone (GH) and causes appetite. Scientists developed synthetic drugs like Hexarelin, which seem to act like ghrelin, over 25 years ago. Since then, ongoing research and studies have been conducted to investigate the outcomes and potential uses of these peptides.
What does Hexarelin peptide do? Hexarelin is believed to mimic the action of ghrelin, which activates ghrelin receptors in the body, especially in the pituitary gland and hypothalamus. These receptors, which are growth hormone secretagogue receptors (GHS-Rs) and, more specifically, GHSR-1a, play a role in stimulating the release of growth hormone (GH). Through the activation of these receptors, Hexarelin can function as a growth secretagogue (GHS).
GHSR-1a receptors are not limited to the hypothalamus and pituitary gland; they also can be found throughout the nervous system and other tissues. Because of this, Hexarelin effects involve both direct stimulation of GH secretion from the pituitary and indirect effects via the hypothalamus. The binding of this peptide to these receptors is thought to cause significant changes that activate internal signaling pathways, many of which rely on G-proteins.
This can include protein kinase C (PKC) activation, which amplifies the signal and facilitates GH release from pituitary cells. Repeated administration of Hexarelin may, however, result in temporary receptor desensitization, which can last for days or weeks. Now, let’s see what is Hexarelin used for?
Three groups of research models at different stages of development and age participated in the study to determine the potential of Hexarelin in stimulating the secretion of growth hormone (GH).
Hexarelin, GHRH alone, or GHRH in combination with arginine was given to all three groups. In adolescent models, GH levels increased significantly with the GHRH + arginine combination. In elderly models, Hexarelin did increase GH levels more than GHRH alone but less than GHRH + arginine combination. These findings demonstrated that Hexarelin can optimize GH levels in young and adult models, while its effect in older models may be minimal.
Another study examined the Hexarelin effect on GH1 murine tumor cells, which were supposed to be unresponsive to GHRH. The researchers tested Hexarelin on rat pituitary normal cells and GH1 tumor cells. They observed that GHRH increased the release of GH in the normal cells but not in the tumor cells. Unexpectedly, when Hexarelin was administered, GHRH was still unable to induce additional GH release, suggesting that Hexarelin and GHRH might have different mechanisms.
This distinction suggests that growth hormone-releasing peptides (GHRPs), such as Hexarelin, can stimulate cells that are not responsive to GHRH. The researchers stated, “In this latter cell model, GHRH and Hexarelin seemed to have stimulatory effects on GH secretion,’’ meaning that their different mechanisms can cause complementary and perhaps synergistic GH production when both agents are used in combination.
Research has also shown that Hexarelin has cardiovascular benefits. In animal studies, an isolated dose of Hexarelin appeared to improve heart function, increasing the left ventricle ejection fraction (LVEF) without altering blood pressure. In models with compromised coronary artery flow, Hexarelin was reported to increase cardiac output and arterial pressure without altering heart rate. Studies on ischemic rat hearts also suggested that Hexarelin can help restore the electrical activity of the heart, reduce cell death, and support overall heart cell survival.
In another experiment, scientists administered Hexarelin daily to myocardial mouse models. They noticed that this peptide has the potential to boost stroke volume and cardiac output, while decreasing peripheral vascular resistance.
One study investigated whether body composition, in terms of fat mass, played a role in the action of Hexarelin on GH release. It was found that individuals with higher fat mass had a blunted GH response to Hexarelin administration. Gender, on the other hand, appeared not to have a strong effect on the quantity of GH released, suggesting that fat mass might be the more significant factor for the modulation of Hexarelin’s effects.
Early studies also indicate that Hexarelin acetate can help protect muscle tissue under catabolic stress; in a test, subjects exposed to muscle-wasting conditions lost approximately 12% of muscle mass. Those injected with Hexarelin, however, lost only about 7% of their weight. Subsequent studies duplicated these findings, which show that Hexarelin can also maintain muscle strength when the body is exposed to catabolic agents.
References:
Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656-660. doi:10.1038/45230
Bisi G, Podio V, Valente F, et al. Effects of hexarelin on GH secretion in elderly subjects. J Endocrinol Invest. 1999;22(11):783-787. doi:10.1007/BF03343649
Isidori A, Lo Monaco A, Cappa M. A study of Hexarelin and GH release in humans. Eur J Endocrinol. 1998;139(6):552–557. doi:10.1530/eje.0.1390552
De Gennaro Colonna V, Rossoni G, Bernareggi M, et al. Hexarelin, a growth hormone releasing peptide, improves cardiac performance in heart failure. Eur J Pharmacol. 1997;328(1):131-136. doi:10.1016/S0014-2999(97)89630-6
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