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Sermorelin (a.k.a. Geref, GHRH (1-29)) is a synthetic analogue of human growth hormone releasing hormone (GHRH). It acts like endogenous HGRH to cause the release of growth hormone (GH) from the anterior pituitary. Recent studies suggest that sermorelin may provide many of the benefits of GH injections without as many side effects.pituitarygland


The Side Effects of Growth Hormone
Numerous animal studies have demonstrated that while GH can eliminate or reduce the symptoms associated with endogenous GH deficiency, they may produce undesirable effects as well. The problem arises from the fact that GH injections don’t mimic the normal GH release patterns. Under normal circumstances, GH release is tied to an individual’s normal sleep-wake cycle as well as to patterns of eating and exercise. Additionally, levels of the hormone tend to rise and fall in a smooth manner under normal circumstances. Animal studies have shown that injection of GH does not produce normal timing or the same gentle rise and fall in hormone levels. Furthermore, exogenous GH is not subject to normal feedback mechanisms.


The net results of the non-physiologic administration of GH are headaches, increased risk of diabetes, increased risk of cancer, and tachyphylaxis (reduced efficacy of GH over time). To avoid these side effects, administration of GH in a more physiologic manner is necessary. Unfortunately, physiologic administration of exogenous GH cannot not easily be achieved.


Sermorelin as an Alternative to GH


Sermorelin is a synthetic version of GHRH, the hormone responsible for controlling physiologic release of Growth Hormone. Unlike exogenous GH, exogenously administered sermorelin is regulated by many of the body’s natural feedback mechanisms. The result of this regulation is that sermorelin produces GH release that is very similar to what would occur in the body under normal physiologic circumstances.


Most important among the effects that sermorelin mimics is the preservation of episodic (intermittent) GH release. GH release secondary to sermorelin is governed by sleep-wake cycles, eating, and exercise. The preservation of normal GH physiology reduces risks of diabetes and cancer associated with exogenous GH administration. It also reduces the incidence of tachyphylaxis, which means that the response to sermorelin does not diminish over time as it does with direct GH injection[1].




[1] R. F. Walker, “Sermorelin: A better approach to management of adult-onset growth hormone insufficiency?,” Clin. Interv. Aging, vol. 1, no. 4, pp. 307-308, Dec. 2006.checkout latest news and information at



Modified GRF (1-29), called mod GRF for short, is an analogue of human growth-hormone releasing hormone (GHRH). GHRH, which is produced by the hypothalamus, causes the release of growth hormone from the anterior pituitary. Growth hormone (GH), in turn, affects various end-organ receptors to stimulate muscle growth, bone growth, calcium retention, and a host of other things.


The GHRH-GH Axis and Modified GRF (1-29)


The GHRH-GH axis is the technical term applied to the system of hormones and organs that regulate and respond to growth hormone. The entire process starts in the hypothalamus, a small region of the brain that sits just above the brain stem. The hypothalamus produces a number of hormones, one of which is referred to as growth-hormone releasing hormone (GHRH). GHRH acts on the pituitary gland, which sits just below the hypothalamus, causing it to release growth hormone. Growth hormone then goes on to affect liver, bone, fat, muscle, and thyroid tissues.


GHRH and GH hormone levels are regulated by feedback from the various organs that GH affects. For instance, a rise in levels of Insulin-like growth factor 1 (IGF-1) will suppress GH and GHRH production in the pituitary and hypothalamus, respectively.


The regulation of GHRH and GH is complex and subject to a number of positive and negative feedback mechanisms. These mechanisms serve to regulate GH levels and to ensure proper development of body tissues. Exogenous (outside of the body) analogues of GHRH have all of the same effects of GHRH, but are not subject to the feedback mechanisms that normally regulate GHRH.


Mod GRF is similar to GHRH, but is only 29 amino acids long rather than 44 amino acids long. Mod GRF has the same effects as GHRH, even though it is smaller. The molecule itself has been heavily manipulated to increase its half-life, prevent degradation, and increase potency. Mod GRF (1-29) comes in DAC and no-DAC forms. DAC, or Drug Affinity Complex, is a protein that is added to the end of a molecule to prevent it from degrading in the bloodstream of test animals. Modified GRF (1-29) with DAC is known as CJC-1295 – DAC while standard modified GRF (1-29) is known as CJC 1295 – no DAC. So, how do you buy modified GRF (1-29).


Receptor Binding


The primary function of GHRH and any analogue of it is to bind to GHRH receptors (GHRHRs) on the anterior pituitary gland. Binding, in turn, causes the release of GH. Analogues of GHRH can be manipulated by scientists to alter their effects and their durations of action. Mod GRF (1-29) is just one of several analogues that have been created and modified in order to produce varying effects on GH release.


Effects of Growth Hormone


GH has a number of biological actions. In fact, GH has so many functions in mammalian physiology that they haven’t all been uncovered yet. A few known effects include


The above effects of growth hormone lead to decreased LDL (bad) cholesterol, increased muscle and bone mass, increased aerobic capacity, increased fat burning, and even improvements in cognitive function. These effects have all been seen in both animal and human subjects who had GH replacement after being diagnosed with growth hormone deficiency.…

In 2011, biotechnology startup Arrowhead Research developed a peptidomimetic drug that was capable of inducing rapid weight loss in mice. The drug worked by killing blood vessels, but was specific only to blood vessels in white adipose tissue. Adipotide was approved for phase 1 clinical trials by the FDA, but then Arrowhead Research fell off of the radar completely. What, exactly, is Adipotide and why did Arrowhead Research seemingly abandon its early clinical trials?

Adipotide the Peptide

Adipotide is a peptide (protein) of sequence CKGGRAKDC-GG-D (KLAKLAK) 2 . It belongs to a class of peptides known as petidomimetic. That simply means that Adipotide is a shortened version of a much larger protein, but that it produces similar effects to its larger counterpart.

To understand how Adipotide works, it is necessary to understand what has become known as vascular “ZIP codes.” Researchers at the University of Texas MD Anderson Cancer Center identified specific receptor distributions throughout human vasculature (blood vessels). Some receptors are found in multiple locations, but others are highly limited to specific regions. Those receptors that are limited to specific regions act like ZIP codes, identifying those vascular regions as unique from other vascular regions in the body1 .

One region that contains unique receptors is white adipose tissue, more commonly known as fat. In fat tissue, there is a receptor known as the prohibitin/annexin A2 receptor. Prohibitin is an interesting protein that is coded for in the BRCA1 region of chromosome 17 (the same BRCA1 associated with breast and ovarian cancer). It turns out that prohibitin is a tumor suppressor gene, which means that, when expressed correctly in healthy adults, prohibitin prevents cancer from arising.

Prohibitins have derived their name from the fact that they prohibit cancer growth. As it turns out, they inhibit cancer growth in several different ways, one of which is to prevent blood vessel growth through programmed cell death. Adipotide has similar effects in prohibiting blood vessel growth and is specific to the prohibitin/annexin A2 receptor. This means that Adipotide only prevents growth of blood vessels found in white fat. Without a blood supply, fat cells die and thus weight loss is achieved. Get related reviews at this link.

Adipotide Studies

Studies in both rats and obese monkeys have found that Adipotide causes apoptosis in blood vessels suppling white fat. Apoptosis is a process in which cells die in an ordered, controlled fashion. Experimental animals thus show a marked loss in white adipose tissue and concomitant weight loss2,3 . Additionally, the animal subjects showed improvements in insulin resistance, meaning that they became less prone to diabetes as a result of losing so much adipose tissue.

Current Status

Thought the hype around Arrowhead Research on Wall Street died back (as was the case with Wall Street and many biotechnology firms), the company has remained strong and continues to investigate the benefits of Adipotide in both obese patients and cancer patients. A phase 1 clinical trial is currently underway at the MD Anderson Cancer Center in Houston. Treatment will involve 39 obese prostate cancer patients and three different dose levels of the drug4 .



1. Blood vessel mapping reveals four new ‘ZIP codes’. at <>

2. Barnhart, K. F. et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci. Transl. Med.3, 108ra112 (2011).

3. Kolonin, M. G., Saha, P. K., Chan, L., Pasqualini, R. & Arap, W. Reversal of obesity by targeted ablation of adipose tissue. Nat. Med.10, 625-632 (2004).

4. Arrowhead Research Corporation | Adipotide. at <>…