Fragment 176-191 is a small peptide that comprises the last 15 amino acids (AAs) from the c-terminal end of growth Hormone (hGH)¹. During childhood, hGH plays a critical role in growth regulation. However, in adulthood, hGH’s most well-known function is metabolic. Among other actions, hGH stimulates insulin-like growth factor-1 (IGF-1) production and release^2-4. In addition, the release of hGH from the anterior pituitary gland is stimulated by hypothalamic growth hormone-releasing hormone (GHRH)⁵.

Fragment 176-191 and similar hGH fragments have powerful lipolytic and anti-lipogenic properties that have drawn researchers’ interest for decades^6,7. Early investigation showed that injecting rats with c-terminal fragments of hGH caused a temporary increase in blood glucose and a more persistent boost in plasma insulin. Interestingly, fragments that did not contain AAs 178-191 had no effect. This provided crucial early evidence suggesting a minimum required sequence for a peptide to be biologically active⁷.

Later research found that both hGH and the slightly truncated fragment 177-191 could cause weight loss in mice by promoting lipolysis, although a previous report suggests that it inhibits lipogenesis instead^8,9. Additionally, this study indicated that this is because the peptide sequence can boost the production of beta-3 adrenergic receptors (ADRB3)⁸. Interestingly, it does not appear that fragment 177-191 acts on hGH receptors and, unlike hGH, does not stimulate cell proliferation⁶. These results add to the body of evidence suggesting that hGH may be a prohormone with differentially truncated forms that have their own effects^6,10. Finally, fragment 177-191 co-injected with hyaluronic acid (HA) reduced cartilage degeneration and the degree of motor disability in a rat osteoarthritis model¹¹.

These results highlight the utility of fragment 176-191 and related peptides as valuable research tools. Although a phase 2B clinical trial investigating fragment 177-191 as a treatment for obesity stalled, hGH c-terminal fragments provide means to manipulate lipid metabolism in the lab without the interfering factors of IGF-1 signaling alterations or GH receptor^6,12. This specificity could one day help researchers uncover novel mechanisms and future therapies.

1. Wade JD, Ng FM, Bornstein J, Pullin CO, Pearce JS. Effect of C-terminal chain shortening on the insulin-antagonistic activity of human growth hormone 177--191. Acta Endocrinol (Copenh). 1982;101(1):10-14.
2. Brinkman JE, Tariq MA, Leavitt L, Sharma S. Physiology, Growth Hormone. In: StatPearls. Treasure Island (FL)2021.
3. Bidlingmaier M, Strasburger CJ. Growth hormone. Handb Exp Pharmacol. 2010(195):187-200.
4. Ayuk J, Sheppard MC. Growth hormone and its disorders. Postgrad Med J. 2006;82(963):24-30.
5. Vance ML. Growth-hormone-releasing hormone. Clin Chem. 1990;36(3):415-420.
6. Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442-1449.
7. Ng FM, Bornstein J. Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Am J Physiol. 1978;234(5):E521-526.
8. Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-5189.
9. Wu Z, Ng FM. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochem Mol Biol Int. 1993;30(1):187-196.
10. Devesa J, Almenglo C, Devesa P. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth? Clin Med Insights Endocrinol Diabetes. 2016;9:47-71.
11. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015;45(4):426-432.
12. Heike Stier EV, David Kenley. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology & Metabolism. 2013;3:7-15.

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