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GHRP6 vs MK 677 vs Ipamorelin: How Do These 3 Growth Hormone Secretagogues Compare To One Another?

Table of Contents
GHRP6 vs MK 677 vs Ipamorelin

Key Takeaways

  • Understanding the central difference between GHRP6, Ipamorelin, and MK 677
  • A full breakdown of GHRP6 and its mechanism of action 
  • What various clinical applications MK 677 has shown and its difference between other compounds; ie peptides
  • Ipamorelin in its entirety and what researchers’ studies have shown
  • An in-depth compare/contrast of how GHRP-6, MK677, and Ipamorelin work 

What Are GHRPs and MK 677

Growth hormone-releasing peptides (GHRPs) are synthetic peptide molecules that stimulate the pituitary gland to release of growth hormone. 

They were first developed in the early 1980s when researchers observed the ability of hexarelin—a naturally occurring peptide found in the stomach cells of pigs—to release growth hormone. This led to ongoing studies of GHRPs.

In 1987, a study was published demonstrating that a synthetic GHRP called GHRP-6 could effectively stimulate the release of growth hormone in rats.

This initial research spurred further investigations into GHRP activity, with subsequent studies investigating various GHRPs and their effects on test subjects.

The 1990s saw continued research into GHRPs as potential clinical solutions for a variety of diseases and disorders. The first studies to investigate GHRPs in growth hormone deficiencies.

These studies demonstrated that GHRP administration increased growth hormone levels, suggesting that it could be used to treat subjects of various ages with growth hormone deficiency.

In addition, other studies investigated the effects of GHRP administration on body composition and cognitive function.

Studies showed either MK-677 or Ipamorelin showed signs of their positive effects on body composition, while another study found that administering GHRP-6 to rats resulted in improved memory retrieval and extinction Growth hormones secretagogues have come a long way since their initial discovery over thirty years ago. 

In this article, we will be dissecting each of the compounds separately for the various reasons researchers are continuing their studies on these compounds.

Each compound, GHRp6, MK677, and Ipamorelin are GHSs (Growth Hormone Secretagogues). However, they are not the exact same in terms of what they seem to offer and how they work inside the test subjects spoken of here. We will be highlighting the key differences and similarities.

GHRp6

GHRp6 is a synthetic peptide that acts as a growth hormone-releasing hexapeptide (GHRH). It is a member of the growth hormone-releasing peptide family and works by stimulating the ghrelin receptor, which then releases growth hormones from the pituitary gland.

GHRp6 has shown potential in several applications within testing and was the first of its GHRP family to be tested on subjects with various conditions.

Mechanism Of Action

GHRp6 stimulates the release of growth hormone by binding to the ghrelin receptor. The activation of the ghrelin receptor leads to an increase in intracellular calcium levels and appetite, which then alerts the pituitary gland to release growth hormone.

The effect on appetite is partially mediated by the activation of neuropeptide Y (NPY) release in the hypothalamus.

This mechanism of action makes GHRp6 a selective GH secretagogue, as it only stimulates growth hormone release and does not affect the secretion of other hormones. 

Clinical Applications

Reduced Inflammation

GHRp6 has been researched for its assets, even beyond changes of growth hormone deficiency. In a study examining the peptide’s potential in reducing inflammation, it was discovered that GHRp6 can reduce inflammation in the lungs. This makes the peptide an attractive target for research related to lung inflammation.

Appetite

GHRp6 has been studied for its effect on appetite regulation. The growth hormone-releasing peptide 6 (GHRP-6) is being studied in relation to eating disorders due to its ability to its effects on appetite and food intake.

Growth Hormone Deficiency

This particular study was aimed at investigating the in-vivo actions of the synthetic growth hormone-releasing peptide (GHRP-6). The study showed that GHRP-6 increased serum GH concentrations, which peaked at 30 minutes and declined gradually toward baseline levels after 120 minutes.

Additionally, GHRP-6 induced a significant increase in plasma cortisol levels, which peaked at 60 minutes and returned to baseline at 120 minutes. The study concluded that GHRP-6 is a potent synthetic GH secretagogue that stimulates GH release from the pituitary gland and will be studied further in clinical settings in relation to GH deficiency, abdominal obesity, and cachexia in subjects in the future.

Another example of GHRP-6 in a clinical setting, published in 1996, found that GHRP-6 resulted in a significant increase in GH levels compared to placebo, with the highest levels observed 30 minutes after administration.

Additionally, GHRP-6 administration also led to an increase in cortisol secretion. Researchers in the study concluded that GHRP-6 is a potent GH secretagogue that can stimulate GH secretion while also increasing cortisol secretion in healthy subjects.

Bone density

In this experiment, Ipamorelin, GHRP-6, and GH (Growth Hormone) were combined.The study had the objective to examine whether the growth hormone secretagogues, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in female rats. The rats were administered IPA, GHRP-6, growth hormone (GH), or a vehicle for 12 weeks.

The results showed that all testings increased the rats body weight and total tibial and vertebral BMC measured by DXA. However, total BMC corrections for the increase in body weight were unaffected.

Tibial area bone mineral density (BMD) was increased, but total and vertebral area BMDs were unchanged. In vitro, measurements revealed that the increase in cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged.

The study concluded that IPA and GHRP-6 increased BMC as measured by DXA in vivo, but the increases in cortical and total BMC were due to increased bone dimensions, whereas the volumetric BMD was unchanged.

MK 677

MK677 is a non-peptide growth hormone secretagogue that mimics the effects of ghrelin, a natural hormone that regulates energy balance, metabolism, and the distribution of body fat.

It works by signaling the pituitary gland to release growth hormone, which then travels through the bloodstream to bind to growth hormone receptors in various tissues. 

Mechanism Of Action

MK 677 works by binding to the ghrelin receptor, a receptor found primarily in the brain and pituitary gland. This binding stimulates the secretion of growth hormone (GH) from the pituitary gland, resulting in increased circulating levels of GH in the body.

GH has various effects on the body, including promoting an increase in lean body mass, reducing body fat, and improving bone density. In addition to its effects on GH release, MK 677 also activates the secretion of insulin-like growth factor 1 (IGF-1), which plays a role in cell growth, replication, and repair.

Overall, the mechanism of action of MK 677 involves stimulating the production and release of GH which then activates multiple pathways in the body leading to varying effects such as an increase in bone density, muscle mass, and cognitive function.

Clinical Applications

Growth Hormone Deficiency (Ex: 1)

The study examined the effects of MK-677, a GH-releasing peptide mimic, on the GH/IGF-I axis in nine GH-deficient subjects. Subjects were given 10 or 50 mg MK-677 or a placebo for four days in an ascending-style double-blind study.

The results showed that MK-677 increased serum IGF-I and 24-hour mean GH concentrations in all subjects with no significant adverse effects. MK-677 treatment also increased IGF binding protein-3 concentrations.

Researchers from this study concluded that oral GHRP-mimetic compounds such as MK-677 may have a positive influence on GH deficiency. However, the clinical significance of the observed changes in insulin and glucose levels needs to be assessed in longer-term studies.

Growth Hormone Deficiency (Ex:2)

This chapter discusses the regulation of growth hormone (GH) secretion and its decline with aging, nutrition, feedback from insulin-like growth factor-I (IGF-I), and changes in body composition.

With age, there is an increase in intra-abdominal fat, which is closely related to the decrease in GH secretion. Four potential mechanisms for this decline in GH secretion include diminished GH-releasing hormone (GHRH) release, increased release of somatostatin, enhanced sensitivity to IGF-I feedback, and decreased somatotroph mass. However, there is little evidence of changes in sensitivity to IGF-I feedback or somatotroph cell mass with aging.

Growth hormone-releasing peptide (GHRP) can stimulate the GH axis by activating the GHRP/GH secretagogue receptor. Orally active MK-677, can restore GH secretion toward that seen in young adults and enhance GH secretion in GH-deficient adults. This suggests that GH secretagogues may have a role in short stature in subjects GH deficiency as well as potentially regulating body composition in older subjects. Learn more about if MK 677 makes you taller.

Diet induced Catabolism

The study investigated whether MK-677, an orally active GH-releasing peptide mimic, can reverse diet-induced protein depletion. Eight healthy volunteers were given a calorie-restricted diet with either oral MK-677 or a placebo for two 14-day periods.

During the second week, the mean daily nitrogen balance was significantly improved in the MK-677 group compared to the placebo group with no threatening adverse effects. MK-677 also produced a significant increase in insulin-like growth factor-I concentration .

The study concluded that MK-677 can reverse diet-induced nitrogen depletion, suggesting a role in the treatment of catabolic entities.

Markers of Bone Formation in double-blind study

This study investigated the effect of taking MK-677, an oral growth hormone secretagogue, on markers of bone metabolism in healthy obese males.

The study was a randomized, double-blind, parallel, placebo-controlled trial with 24 obese males aged 19-49 years in two groups: MK-677 (25 mg/day; n=12) and placebo (n=12) for 8 weeks.

The results show that using MK-677 increases markers of bone formation and resorption, such as carboxy-terminal propeptide, procollagen III peptide, and carboxy-terminal cross-linked telopeptide of type I collagen.

Researchers concluded this study demonstrates oral MK-677 can promote healthy bones and potentially reduce the risk of osteoporosis.

Ipamorelin

Ipamorelin is a GHS (Growth Hormone Secretagogue) in the form of a synthesized peptide, which means it stimulates the production of GH.

It is similar to other peptides such as GHRP-2 and GHRP-6 but has more selective activity and fewer potential adverse outcomes.

Ipamorelin is commonly used in combination with other peptides as part of an anti-aging regimen. It has been shown to have a number of outcomes, including increasing muscle mass, reducing body fat, promoting recovery from injuries, improving sleep quality, enhancing skin health, and providing anti-aging effects.

Additionally, ipamorelin has been found to have a positive impact on bone density and brain health. These studies are cited, and the researcher’s claims are explained below.

Mechanism of action

The mechanism of action of ipamorelin involves binding to the ghrelin receptor, which is found in the pituitary gland. This binding stimulates the release of growth hormone (GH) in a pulsatile manner, meaning that GH is released in bursts rather than continuously.

The pulsatile release of GH is thought to mimic the natural patterns of GH secretion. When GH is released into circulation, it promotes the synthesis of insulin-like growth factor-1 (IGF-1) in the liver and other tissues.

IGF-1 is responsible for many of the effects of GH, such as increasing muscle mass, reducing body fat, and promoting bone growth, among others.

The selective activity of ipamorelin at the ghrelin receptor makes it less likely to cause side effects seen with other GH secretagogues.

Clinical Applications

Bone Growth

A study examining the effects of ipamorelin, on adult female rats found that it dose-dependently increased longitudinal bone growth rate (LGR), as well as body weight.

The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption. There was a marginal reduction in plasma GH response after a provocative i.v. dose of ipamorelin, but the pituitary GH content was unchanged .

This study suggests that ipamorelin may have potential in the treatment of children with growth deficiency, but further clinical studies are needed.

Stimulation of Insulin Release

The goal of the study is to examine how ipamorelin, a substance that stimulates the release of growth hormone, affects insulin secretion in normal and diabetic rats by studying the pancreatic tissue fragments.

The results revealed that ipamorelin enhances insulin secretion in both normal and diabetic rats, suggesting that it can stimulate the release of insulin through the calcium channel and adrenergic receptor pathways.

This study’s findings provide insight into the potential use of ipamorelin in the treatment of diabetes, however, further research is required to determine its efficacy and safety for this purpose.

Ipamorelin’s Effect On Somatotrophs

Somatotrophs, a specialized group of cells in the anterior pituitary, are responsible for the secretion of Growth Hormone (GH). This study’s primary objective was determine the effects of Ipamorelin, a growth hormone secretagogue, on the composition of somatotroph cells and their GH content.

The investigation included an in vitro examination of pituitary cell cultures from female rats subjected to a 21-day Ipamorelin regimen. The study showed that Ipamorelin led to an increase in the volume density of secretory granules and an increase in the proportion of somatotroph cells in vitro. They did this while preserving the equilibrium between strongly and weakly immunostained GH cells.

Furthermore, it was observed that the basal intracellular GH content within somatotroph cells over a span of 4 hours was lower in the Ipamorelin-treated group in comparison to the saline-treated group. However, Ipamorelin initiated a subsequent surge in intracellular GH content.

These findings collectively suggest that Ipamorelin possesses the capacity to exert a dynamic regulatory influence over the somatotroph population and the GH hormone content, specifically in young female rats.

How do GHRP-6, MK677, and Ipamorelin Compare?

GHRP-6, MK677, and Ipamorelin are three synthetic peptides with GH-releasing properties that can promote muscle growth, fat loss, and anti-aging.

While all three have some similarities in their mechanisms of action, potency, and potential outcomes from a clinical perspective, they also have some significant differences in terms of selectivity and side effects.

By making these comparisons from an analytical perspective, researchers can determine which compound best suits their research study.

    Key differences

    The key differences between GHRP6, MK677, and Ipamorelin include their potency, selectivity, mode of administration, and potential.

    GHRP6 is considered to be less selective and less potent than the other two peptides. It has a lower affinity for the ghrelin receptor and can produce more negative side effects. 

    MK677 is highly potent and more selective than GHRP6, meaning it produces fewer negative side effects and may be better tolerated. It’s also orally consumed, which makes it more convenient than GHRP6. 

    Ipamorelin is highly selective and less potent than MK677, leading to fewer negative side effects. In terms of administration, GHRP6 is typically injected, while MK677 and Ipamorelin can be administered to subjects orally. 

    This is seen as an easier option in a clinical setting than several injections daily as GHRp6 would need to be administered.

    Similarities

    While GHRP6, Ipamorelin, and MK677 for sale online have differences in their potency and selectivity, they share several key similarities. All three peptides are synthetic growth hormone secretagogues that stimulate the release of growth hormone from the pituitary gland. 

    They work by binding and activating the ghrelin receptor, which is involved in regulating appetite, energy homeostasis, and GH secretion. Secondly, GHRP6, MK677, and Ipamorelin all have potential therapeutic uses related to muscle growth, fat loss, and anti-aging. 

    They have been studied for their effects on bone density, wound healing, sleep quality, and cognition, among other outturns. 

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