GHRP-6 and Melanotan

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GHRP-6 is a synthetic ghrelin receptor agonist that causes growth hormone (GH) release with Melanotan 2. Ghrelin also causes GH release and is a known appetite stimulant. New research suggests that GHRP-6 affects the ghrelin receptor differently in the presence of both insulin and food and has helped explain why food alters the function of GHRP-6


GHRP-6 and Insulin


Early studies indicated that ghrelin stimulates the release of insulin in both normal and diabetic rats[1]. Insulin is one of many factors that impact GH release. In general, insulin release increases GH levels. Studies investigating the combined roles of insulin and GHRP-6 on GH levels have shown that taking the two together produces a much greater GH release than if either protein is taken alone[2]. It would seem follow that food consumption, which is associated with increased insulin levels, would also boost the GH response to GHRP-6. The opposite is true.


GHRP-6 and Food


The consumption of food, particularly carbohydrates and fats, blunts the GH response to GHRP-6. In other words, GH levels rise more when GHRP-6 is taken without food. Fasting induces GH production, leading to more frequent pulsatile release from the anterior pituitary. It also increases the amount of GH released with each pulse[3]. Anything that increases blood sugar levels, like eating, will suppress GH[4].


GHRP-6 is an analogue of ghrelin and ghrelin is secreted when blood sugar levels drop. Ghrelin, insulin, and GH can thus be thought of as blood sugar regulators. Ghrelin and GH act to increase blood sugar levels while insulin acts to lower them. Low blood sugar stimulates ghrelin and GH release and suppresses insulin release. When GHRP-6 is taken with insulin and without eating, the effect on GH levels is amplified by low blood sugar levels. Under normal circumstance (i.e. insulin levels increase in response to food intake), the opposing effects of blood sugar levels and insulin on GH result in a blunted response.


The Basic Fact


Food consumption during the administration window for GHRP-6 causes a blunted GH response. GHRP-6 administered to mice produces greater GH secretion when use with insulin at least partially because insulin lowers blood sugar. Fasting will also boost the GH response to GHRP-6.




[1] E. Adeghate and A. S. Ponery, “Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats,” J. Neuroendocrinol., vol. 14, no. 7, pp. 555-560, Jul. 2002.

[2] A. Peñalva, A. Carballo, M. Pombo, F. F. Casanueva, and C. Dieguez, “Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man,” J. Clin. Endocrinol. Metab., vol. 76, no. 1, pp. 168-171, Jan. 1993.

[3] K. Y. Ho, J. D. Veldhuis, M. L. Johnson, R. Furlanetto, W. S. Evans, K. G. Alberti, and M. O. Thorner, “Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man.,” J. Clin. Invest., vol. 81, no. 4, pp. 968-975, Apr. 1988.

[4] J. F., “Fasting and Growth Hormone Physiology – Part 3,” Intensive Dietary Management. .

Growth Hormone and IGF-1 Stimulation by CJC-1295

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Some synthetic proteins that mimic the effects of normal hormone cascades while others produce non-physiologic, but ultimately useful changes in those same cascades. In the case of CJC-1295 and Sermorelin, both growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels are stimulated to supra-physiologic levels in animal studies. Studies also show that careful administration of CJC-1295 can produce beneficial effects in GH-deficient rodents precisely because it creates a non-physiologic hormone response.


CJC-1295 and Growth Hormone Levels


Administering a single dose of CJC-1295 to mice produces a 2- to 10-fold increase in serum levels of GH, an effect that lasts for about six days. In this situation, peak GH levels are directly related to the size of the dose of CJC-1295 administered. Maximum levels of GH are reached about two hours after administration of CJC-1295 and then diminish slowly over time.


Multiple injections of CJC-1295 affect peak GH levels in mammals only if administered in rapid succession (i.e. they mimic a single bolus). Under no circumstances do multiple injections affect normal physiologic fluctuations in GH levels (the ebb and flow patterns of GH levels). With CJC-1295, GH peaks and troughs occur with regular timing, but with different set levels. The physiology is preserved, but a supra-physiologic level of GH is achieved.


CJC-1295 and IGF-1 Levels


Unlike GH, animal studies demonstrate that IGF-1 levels continue to rise with repeated administration of CJC-1295 over time. This progressive effect produces a higher IGF-1 peak with each successive CJC-1295 administration. Repeated administration also shortens the time required to reach the IGF-1 peak, such that the peak is reached more quickly with each successive injection[1]. Animal studies have not demonstrated any adverse effects from the non-physiologic IGF-1 stimulation, but the change in IGF-1 physiology may make CJC-1295 an excellent protein for studying both the short-term and long-term effects of IGF-1 stimulation on everything from growth and healing to blood sugar levels and liver function.


The Bottom Line


CJC-1295 is a useful analog of growth hormone releasing hormone (GHRH) that has long-term effects on both GH and IGF-1 levels. Its long duration of action makes CJC-1295 an ideal peptide for research studies as it can be administered in a convenient, once-per-week manner. The net results of once-per-week dosing of CJC-1295 are increases in both GH and IGF-1 levels.




[1] S. L. Teichman, A. Neale, B. Lawrence, C. Gagnon, J.-P. Castaigne, and L. A. Frohman, “Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults,” J. Clin. Endocrinol. Metab., vol. 91, no. 3, pp. 799-805, Mar. 2006.

What is Ipamorelin

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Ipamorelin is an agonist of the ghrelin receptor (a.k.a. growth hormone secretagogue receptor) and thus induces the anterior pituitary gland to secret growth hormone (GH). Like many growth hormone secretagogues, ipamorelin significantly increases plasma (blood) levels of GH in mammals. Unlike other growth hormone secretagogues, ipamorelin is almost exclusive in stimulating GH secretion without affecting other hormones.


Ipamorelin Lacks Significant Side Effects


Some synthetic proteins designed to target Growth Hormone have been known to stimulate the production of prolactin, follicle-stimulating hormone, and luteinizing hormone. Stimulation of these hormones can lead to a number of undesirable side effects, such as breast growth in men and changes in menstruation for women. Ipamorelin has none of these effects. Additionally, it does not affect thyroid-stimulating hormone levels as some growth hormone secretagogues do.


buy-ipamorelinCertain ghrelin receptor agonists can impact adrenocorticotropic hormone (ACTH) and cortisol levels. Ipamorelin has shown no such effects when tested in swine, even at doses 200 times higher than what are needed for maximal GH release. There is no concern for fatty tissue deposition, skin issues (e.g. darkening, thinning, etc.), or type 2 diabetes with ipamorelin[1].


An Apt Comparison


The only other hormone that is more selective for GH release than ipamorelin is the endogenous growth hormone releasing hormone (GHRH). Ipamorelin is just as effective in producing GH release, without significant side effects, as GHRH. In fact, it would be virtually impossible to tell using GH levels and side effects whether GHRH or ipamorelin had been administered in a clinical setting.




[1] K. Raun, B. S. Hansen, N. L. Johansen, H. Thogersen, K. Madsen, M. Ankersen, and P. H. Andersen, “Ipamorelin, the first selective growth hormone secretagogue,” Eur. J. Endocrinol., vol. 139, no. 5, pp. 552-561, Nov. 1998.