Modified GRF (1-29) and HGH Synthesis

Overview of Modified GRF (1-29)

Modified GRF (1-29) is a modified version of GRF (1-29), the smallest amino-acid sequence from the original GHRH that may still retain the ability to trigger the receptors in the pituitary gland and induce an HGH spike. As the name suggests, GRF (1-29) and modified GRF (1-29) are made of 29 amino acids. However, Modified GRF (1-29) has 4 of the original 29 amino acids replaced with the intention to make the peptide more resistant to rapid cleavage by the enzyme dipeptidyl peptidase-4. This cleavage was previously reported to result in peptide inactivation.^[1] More specifically, the replaced amino acids are the 2nd, 8th, 15th, and 27th amino acids.

Due to this replacement, the peptide is also known as tetrasubstituted GRF (1-29), and its sequence is Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg. As a result, the half-life of the peptide has been anticipated to last from 10 – 30 mins.  One of the main modifications is the replacement of L-alanine with D-alanine in the 2nd spot.^[2] According to the researchers, “the disappearance half-time of the D-Ala2 analog was 6.7 +/- 0.5, whereas that of GHRH-(1-29)-NH2 was 4.3 +/- 1.4 min (P < 0.05). These findings demonstrate that the D-Ala2 substitution contributes to the enhancement of biological activity by reducing metabolic clearance.“

Research

Mod GRF (1-29) was developed to have a longer half-life but retain identical effects to GRF (1-29), also known as Sermorelin. Since no studies investigate the effects of modified GRF (1-29) without DAC, the following reports will be based on GRF (1-29) research.

Mod GRF (1-29) and HGH Synthesis & Growth

Researchers have reported GRF (1-29) to have the potential to increase HGH pulse synthesis.^[3] Repeated dosing may lead to a significant increase in growth hormone levels. The increase in peak HGH levels can lead to various benefits, such as increased growth in children and improved muscle mass, fat loss, physical performance, and energy levels in adults. Research studies have been conducted on children with growth failure, and the administration of the peptide appeared to yield promising results universally. However, further research is needed to confirm the peptide’s overall and long-term effects.

Mod GRF (1-29) and Body Composition

One study focused on the effects of GRF (1-29) administration reported the peptide’s apparent ability to increase growth velocity by 74%, maintained for up to a year of therapy. These findings suggest that GRF (1-29) therapy may be a viable treatment option for children with GHD experiencing growth failure.^[4] A trial conducted in adult males reported that administering GRF (1-29) for a duration of 4 months resulted in a significant increase in lean body mass by 1.26 kg. However, it is important to note that such effects were only observed in male subjects and were not observed in females.^[5] This could be attributed to the fact that GRF (1-29) therapy may not cause human growth hormone (HGH) peaks to exceed the physiological limits, which may differ between genders due to biological variations. For example, as the growth hormone remains within its physiological limits in women, it is still significantly impacted by the negative effect of estrogens on IGF-1 production, the main anabolic mediator of HGH.^[6] Researchers reported that estrogen affects the HGH-IGF-1 axis “by decreasing liver secretion of insulin-like growth factor-I (IGF-I).“

GRF (1-29) may also cause fat loss, especially around the abdomen, due to its potential HGH-boosting effects. A study involving 19 participants across different age groups found that 2 weeks of GRF (1-29) therapy could improve their waist-to-hip circumference ratio.^[7]

Mod GRF (1-29) and HGH-Related Benefits

A study investigating the effects of GRF (1-29) in older adults found that it might lead to significant improvements in strength and endurance levels.^[8] This trial involved 11 participants, who exhibited an increased capacity for performing crunches and improved shoulder pressing strength after receiving GRF (1-29) therapy. These findings suggest that GRF (1-29) may be a promising therapy for improving physical function in older adults. 

Age-related changes in muscle mass and strength may also result in decreased mobility and quality of life, and interventions such as GRF (1-29) therapy may potentially mitigate these negative effects. Further research is needed to explore the potential benefits and limitations of GRF (1-29) therapy for improving physical performance.

Another HGH-related benefit may be the promotion of skin cell growth and increased collagen deposition within the derma. A study on elderly men and women revealed that a 4-month treatment course of GRF (1-29) administrations appeared to increase skin thickness significantly.^[9] This finding suggests that GRF (1-29) may play a role in improving skin quality and reducing signs of aging, such as fine lines and wrinkles. Further research is needed to fully understand the effects of GRF (1-29) on skin health. Still, these initial findings are promising for individuals seeking to improve their skin’s appearance and overall health. 

Conclusion

In conclusion, Modified GRF (1-29), also known as tetrasubstituted GRF (1-29), is a synthetic analog of growth hormone-releasing hormone designed to stimulate the release of growth hormone in the body.  The modifications in its amino acid sequence may make it more resistant to rapid cleavage by enzymes and increase its half-life, leading to potential therapeutic uses in various conditions, such as growth hormone deficiency, osteoporosis, and muscle wasting. 

Studies in the unmodified GRF (1-29) show that it may increase HGH synthesis and growth, improve body composition, and have other HGH-related benefits, such as improving physical function in older adults.  However, further research is needed to confirm these findings, especially if they also apply to the effects of Modified GRF (1-29) without DAC. 

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References

1. Scarborough R, Gulyas J, Schally AV, Reeves JJ. Analogs of growth hormone-releasing hormone induce release of growth hormone in the bovine. J Anim Sci. 1988 Jun;66(6):1386-92. doi: 10.2527/jas1988.6661386x. PMID: 3135287.
2. Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. J Clin Endocrinol Metab. 1994 Oct;79(4):1208-11. doi: 10.1210/jcem.79.4.7962295. PMID: 7962295.
3. Achermann JC, Hindmarsh PC, Robinson IC, Matthews DR, Brook CG. The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals. Clin Endocrinol (Oxf). 1999 Nov;51(5):575-85. doi: 10.1046/j.1365-2265.1999.00839.x. PMID: 10594518.
4. Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Eengrand P, Shah S. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab. 1996 Mar;81(3):1189-96. doi: 10.1210/jcem.81.3.8772599. PMID: 8772599.
5. 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.
6. Cook DM. Growth hormone and estrogen: a clinician’s approach. J Pediatr Endocrinol Metab. 2004 Sep;17 Suppl 4:1273-6. PMID: 15506073.
7. 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.
8. 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.
9. 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.