Sermorelin Peptide Potential as a Growth Hormone Secretagogue

Sermorelin Acetate, a synthetic peptide, was developed to function as an analog of a naturally occurring hormone called growth hormone-releasing hormone (GHRH). While GHRH has 44 amino acids, Sermorelin peptide is truncated down to 29 amino acids. Sermorelin peptide is also known as the Growth Hormone Releasing Factor (1-29) or GRF (1-29). Sermorelin is the smallest fragment of the GHRH chain that appears to possess the same functions, namely, stimulating the pulsatile release of human growth hormone (HGH) by the pituitary gland. Due to this potential, Sermorelin peptide has been classified by researchers as a Growth Hormone Secretagogue (GHS). Like GHRH and other GHSs, Sermorelin may increase the production of HGH in the pituitary gland, resulting in higher and more frequent peaks of the growth hormones. This would also result in elevated levels of Insulin Growth Factor-1 (IGF-1), the primary anabolic mediator of the effects of HGH in the human body.

What is the Sermorelin?

Sermorelin was first synthesized in the early 1980s and has been avidly researched since its development. Scientists posit that it has the potential to be used as a provocation test for the diagnosis of pituitary disorders and, more specifically, growth hormone deficiency (GHD). The peptide may also hold potential therapy for growth failure in children. It is made of 29 amino acids and bears the sequence YADAXFXNSYRKVLGQLSARKLLQDXMSR. Sermorelin peptide, aka GRF (1-29), should not be confused with Modified GRF (1-29), which has 4 of the original 29 amino acids replaced with the intent to increase its half-life from 10 to 30 minutes. 

General Research in Sermorelin

Sermorelin Peptide and Endocrine Effects

As a GHRH analog, Sermorelin peptide has been researched primarily for its potential to stimulate pulsatile HGH synthesis via the pituitary gland. Studies observed that as long as the pituitary gland is functioning correctly, Sermorelin, combined with the amino acid Arginine, may induce a significant spike in serum HGH levels.^[1] The researchers also noted that “doses of Sermorelin are well tolerated. Transient facial flushing and pain at the [administration] site were the most commonly reported adverse events.” 

HGH is the primary hormone that regulates growth in children. Clinical trials with growth failure also report that Sermorelin peptide appeared to effectively increase growth velocity with growth failure and functional pituitary glands by 74%.^[2] Further research reported that 6 months of either taking Sermorelin peptide or HGH therapy, appeared to exhibit a similar increase in growth velocity.^[3] Studies also reported an apparent significant increase in serum HGH levels after several days of Sermorelin peptide administration.^[4]

The peptide may also affect the levels of other hormones apart from HGH, such as insulin and sex hormones.  Although high HGH is often associated with increased insulin levels and insulin resistance, one 16-week trial suggested that Sermorelin may improve insulin sensitivity in males but not in females.^[5] The trial participants receiving Sermorelin peptide appeared to have slightly lower glucose levels, potentially due to the increase in IGF-1 and its insulin-like effects. One animal trial also reported an increase in gonadotropic hormones and testosterone levels in male mice, but there is no clinical research to support these findings.^[6] 

Sermorelin Studies in Strength, Endurance, and Cardiovascular Health

Sermorelin may benefit strength, endurance, body composition, and cardiovascular health thanks to its apparent HGH-stimulating effects. In one trial with 9 male participants, researchers reported that 4 months of Sermorelin peptide administration appeared to increase lean body mass by 1.26 kg.^[7] The study also included 10 women, but they were not reported to experience any changes in body composition. The researchers concluded, “These observations suggest that GHRH analog administration induced anabolic effects favoring men more than women. Further studies are needed to define the gender differences observed in response to GHRH analog administration.”

Results from another trial in 11 older adults suggested that Sermorelin peptide appeared to improve their strength and endurance levels significantly.^[8] The participants could perform more crunches and became stronger at shoulder pressing. One study of 19 young and old participants also showed that as little as 2 weeks of Sermorelin peptide therapy appeared to improve the ratio of their waist to hip circumferences.^[9] The waist-hip ratio is an essential indicator of various metabolic and cardiovascular risks. An improved waist-hip ratio may improve various cardiometabolic parameters such as blood pressure.^[10] In fact, in one study of 11 male participants, Sermorelin peptide appeared to be capable of lowering the systolic blood pressure from 135 to 125 mmHg on average. 

Sermorelin Peptide and Skin

Scientists posit that Sermorelin has the potential to function in increasing HGH levels. From this assumption, it may be possible for Sermorelin peptide to increase the proliferation of new skin cells, ultimately leading to increased collagen deposition inside the derma. 

One trial in older men and women reported that 4 months of Sermorelin peptide administration appeared to significantly increase their skin thickness.^[11] Additionally, the men, but not the women, also experienced improved libido. Increasing collagen production in the skin may help combat signs of skin aging, such as reduced skin thickness and elasticity. 

Sermorelin Peptide and the Nervous System

One trial in 23 young individuals suggested that even a one-time administration of Sermorelin peptide may help improve short-term memory.^[12] In fact, the researchers reported that the effect on memory recall appeared more significant in Sermorelin-treated participants than those treated with a placebo. There is also mixed evidence regarding the effects of Sermorelin peptide on brain tumors. One in vitro experiment reports that Sermorelin peptide may speed up the development of neuroendocrine tumors such as pituitary adenomas due to its possible growth-promoting effect.^[13] However, a clinical trial in patients with gliomas reported the opposite effect, observing that the peptide appeared to suppress the recurrence of the tumors.^[14] 

Conclusion

Sermorelin may hold significant research potential as a Growth Hormone Secretagogue (GSH). This is supported by research findings indicating that when administered with Sermorelin, study participants’ serum HGH levels could not exceed the physiological limits exerted by somatostatin. The only adverse effects during therapy are reported to be transitionary local reactions in the administration site, which occur in 1/5 of the patients and include pain, swelling, and redness.

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References

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7. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
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9. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992 Aug;75(2):530-5. doi: 10.1210/jcem.75.2.1379256. PMID: 1379256.
10. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976.
11. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
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14. Chang Y, Huang R, Zhai Y, Huang L, Feng Y, Wang D, Chai R, Zhang W, Hu H. A potentially effective drug for patients with recurrent glioma: sermorelin. Ann Transl Med. 2021 Mar;9(5):406. doi: 10.21037/atm-20-6561. PMID: 33842627; PMCID: PMC8033379.