The effects of GHRP-6 on cell differentiation to myocytes (i.e. myogenesis). From: Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506, reproduced under the terms of the Creative Commons Attribution License

The effects of GHRP-6 on cell differentiation to myocytes (i.e. myogenesis). From: Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506, reproduced under the terms of the Creative Commons Attribution License

Growth hormone releasing peptides (GHRPs) are short molecules developed to mimic the growth hormone secretagogue (GHS, or ghrelin) as the name suggests. Interest in these small sequences began in the early 1980s. At this time, GHRP-6 was regarded as the most potent of these compounds1. GHRP-6 is active at the GHS receptor (GHS-R) and may therefore activate or regulate a number of different pathways in animal systems. Ghrelin and/or GH may mediate effects on metabolism, appetite, cardiac function and/or protection and cell survival. Therefore, GHRP-6 may be a useful reagent in animal models of various conditions, ranging from ischemia to obesity.

GHRP-6 may be administered by injection, topically or orally. However, there are other ghrelin mimetics that may be more effective when administered by the latter route1. Intranasal delivery systems for this peptide have also been proposed2. GHRP-6 has limited stability and availability as a topical treatment, unless modified or conjugated to another small molecule3. One group recently reported improvements in these properties through the conjugation of GHRP-6 to biotin, and that this formulation elicited significantly increased collagen synthesis in cultured skin cells3. The same group then applied this compound to cultured myoblasts, and reported that this treatment resulted in significant increases in their differentiation to myocytes when compared to control cells3. This was thought to be associated with increased collagen-I synthesis3. Treatment with GHRP-6-biotin was also associated with significant increases in intracellular ATP and lactate compared to controls, indicating that treated cells used more energy than non-treated cells3. These findings may align with others that indicate GH may regulate the expression of various genes involved in myoblast differentiation through IGF signaling4.

Many researchers have concluded that GHS and its mimetics also act to prevent apoptosis in a number of cell types5. Apoptosis in pituitary cells, as well as hypothalamic and cerebellar astrocytes, has been observed as a side-effect of diabetes5. This condition may also result in a decrease in GH expression5. Therefore, GHRP-6 may be used in relevant studies to assess the effects of GH or ghrelin on both diabetes and diabetes-induced cell death. A 2011 study compared a daily regimen of either GHRP-6, (150μg/kg) this dose of the same combined with approximately 8IU insulin, insulin alone or a placebo on apoptosis in rats with experimentally-induced diabetes5. Rats with this condition exhibited significantly more apoptosis in the cell types listed above compared to control animals. As individual treatments, GHRP-6 and insulin did not significantly affect cell death after eight weeks. However, the ‘combined’ treatment was associated with significant decreases in apoptosis and in the concentrations of glial fibrillary acidic protein, a marker of nerve cell damage5. GHRP-6 may also enhance the survival of heart muscle cells following experimentally-induced cardiac disease6. A single treatment of 400μg/kg in an animal model of acute myocardial infarction was associated with significant reductions in cardiac injuries and oxidative stress compared to controls6. GHRP-6 may also be used to assess the putative roles of GH in other processes, most notably aging and hormonal dysregulation7.

References:

  1. DeVita RJ. Small molecule mimetics of GHRP-6. Expert opinion on investigational drugs. 1997;6(12):1839-1843.
  2. Pontiroli AE. Peptide hormones: Review of current and emerging uses by nasal delivery. Advanced drug delivery reviews. 1998;29(1-2):81-87.
  3. Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506.
  4. Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocrine reviews. 1996;17(5):481-517.
  5. Granado M, Garcia-Caceres C, Tuda M, Frago LM, Chowen JA, Argente J. Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats. Molecular and cellular endocrinology. 2011;337(1-2):101-113.
  6. Berlanga J, Cibrian D, Guevara L, et al. Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Clinical science (London, England : 1979). 2007;112(4):241-250.
  7. Zouboulis CC, Makrantonaki E. Hormonal therapy of intrinsic aging. Rejuvenation research. 2012;15(3):302-312.