GHRP-6 (Growth Hormone Releasing Peptide-6)

What is GHRP 6

What exactly is GHRP-6? Do we need it in order to survive? Upon reading this, you might be asking yourself these, and other questions, as it pertains to the use of GHRP-6, and your overall health. So, let’s delve into what it is, what it does, and how it is going to affect you, when it is used.

Basically, in its simplest term, GHRP-6 is a synthetic version of ghrelin analogue. Like its counterpart, GHRP-2, GHRP-6 is intended to help in the stimulation of an endogenous growth hormone, GH. This is done within the somatotropins of the pituitary gland (anterior), in both human and animal subjects. This increase can have a major effect on hunger levels, how much food you consume, how much time you will wait between meals, and other factors relating to consumption and hunger levels.

GHRP-6 is specifically intended to help increase the number of somatotropins in the GH pulse. This is accomplished by limiting how much somatostatin is present. This is contrary to standard GHRH, which increases the amplitude in which the pituitary cells will pulse. GHRP-6, unlike ghrelin, isn’t used to help increase appetite, but the secondary action might impact the hypothalamic neurons. Effects can last anywhere from a 1-8-hour window, mimicking the natural application of GH, during a given circulation period.

GHRP-6 Studies

There have been numerous studies utilizing GHRP-6. Many of these studies have shown that biological actions are affected when GHRP-6 is introduced to the test subjects (both human and animal subjects). These actions are similar in nature to those which naturally occur in the hunger-stimulating peptide ghrelin. The main function is to help promote food intake, which is achieved by stimulating hunger. It further aids in energy metabolism.

GH deficiencies can also be treated using GHRP-6. Treating cachexia, and other eating disorders such as obesity, are also achievable using GHRP-6. The met-enkephalin analog is naturally occurring growth factor found in opioids. GHRP-6 also contains D amino-acids, which are synthetic, which lack the opioid activity, and which share zero-sequence relations with GHRH. GHRP-6 has also been shown to lead to the re-stimulation of naturally producing HGH.

Further studies have proven that it can increase IGF-1 secretion by the liver. This has been speculated as being an essential factor required in the anabolic mechanisms, which lead to higher HGH action levels. GHRP-6 has proven to have positive implications for the central nervous system. This is similar in nature to what ghrelin does to helping protect neurons. Among these facts, what might be the most interesting aspect is the fact that GHRP-6 plays various roles in biological functions. From regulating the appetite, to helping improve cardiac function, to aiding in gastrointestinal functions, and increasing the rate at which the metabolism functions, it can greatly benefit users. Further improved behavioral effects have also been linked to use of GHRP-6.

Background: Where does GHRP-6 come from?

Many points in history focused on the study of GHRP-6. Among these points which led to the enlarging ghrelin system were the years of: 1973 and 76, 1982 and 84, 1990, 1996, and 1998-99. During these periods, a series of sequential events occurred. This began with the isolation of somatostatin. This was followed by the discovery of unnatural growth hormone releasing peptides (GHRP). Following this was the isolation of growth hormone releasing hormone (GHRH).

The hypothesis of the natural GHRP form, stemming from GHRH was the next phase in development. Later, GHRH+GHRP synergism in humans was discovered. The discovery of the GH secretagogue (GHS/GHRP receptor) led to the cloning of the receptor. Lastly, the isolation and identification of new, natural engogenous GHRP ghrelin occurred.

All of these events occurred following the talented researchers around the globe who were actively researching the benefits of GHRP-6. The understanding in pharmacology and the physiological regulations of GH secretion is highly attributed to many studies conducted during these years. These understandings stem from the important GHRP discoveries, which show how GH secretion in men, women, and children, was possible. This was discovered, even though it was known that GHRP on its own released GH from the pituitary in-vitro (without adding GHRH). The secretion isn’t dependent on GHRH.

although GHRP was envisioned as a GHRH analog, activity between 1982-84 reflected how the activity of the new hormone regulators, were isolated incidents which could be identified. The intravenous bolus release of GHRP, was found in higher levels in humans, while the opposite was found in-vitro.

GHRP is a form of a pleiotropic peptide, which has a major effect on nutrition, the GH hormone, the metabolism, and in the form of an additional hormone, which when combined with GHRH, works as a new regulator of the pulsatile secretion. A major indication of pleiotropism was noted when an increase in food intake was present by GHRP. Because the contribution was similar, yet different and complementary, it was of high interest to researchers. It played a role in GHRH being able to regulate GH secretion levels.

What was noted was the chemistry makeup of GHRP. It consisted of three chemical classes. These classes were the peptides, the partial-peptides, and the non-peptide forms. All three appear to function via the same receptors and similar cellular mechanism.

GHRPs are active through different administration routes. It is most delivered intravenously (IV) and subcutaneously (SC). However, oral, intracerebroventricularly (IVC), and intranasal administration is also available. These options make for many broad clinical studies into the future. Many evolutionary studies which began with the zebrafish, also showcase the natural receptor hormone underscores the importance of the ghrelin system. GHRPs have been well established and are known to act directly on the pituitary as well as the hypothalamus. This was documented several years prior to the GHS receptor assay.

A final note to consider, is the ghrelin chemical isolation, alongside the identification which was accomplished from the stomach. This was the first, but not the only, major site. Ghrelin became isolated and identified at this point. GRHP action is a continual concern as it relates to GH secretion and regulation. With this in mind, it is increasingly shown to have an indirect and direct effect on the metabolism and nutrition. Further, it effects various other actions, which are both physiological and pharmacological in nature.

GHRP-6: Does it work?

Reactions of both GHRP-6 and GHRP-2 are showcased in the following studies. This is in relation to the release of GH on the pituitary cells. A follow-up study which primarily focused on increasing concentration levels, in an attempt to create a GH dependency, helped better understand dosage restrictions. A major question asked was whether the chemical should or shouldn’t be used in therapeutic sessions in the future.

What the study showed was that GRF, GHRP-2, and GHRP-6 applied in increasing concentration levels, partially helped in purifying sheep somatrophs. This also caused a natural release of GH in the dependent manner. cAMP levels weren’t increased when GHRP-6 was administered. When a combination of GHRP-2 and GRF were administered, it did increase GH and cAMP levels. However, the combination of GHRP-6 and GHRP-2 didn’t increase these levels. In cases of pretreating with adenylyl cyclase inhibitor, an increase in cAMP levels occurred as did GH levels. This was in incidents where GHRP-2 or GRF were applied.

The antagonist didn’t prevent cAMP reactions with application of GHRP-6. In studies where the antagonist was applied to GH receptors, GRP and GHRP-2 combo didn’t increase cAMP rates. Prevention of GH hormone was present when GRPH-2, GRF, and GHRP-6 were applied. In these studies, we learn that GHRP-2 affects the ovine pituitary somatotroph by increasing cAMP concentrations similarly to GRF. A point to note however is that GRF, GHRP-2, and GHRP-6 act differently on the receptors, showcasing why it didn’t affect cAMP levels on the rat pituitary cell cultures.

Studies and research suggest that the circulation of ghrelin is implicated in the regulation between meals. When the levels increase (due to anticipation of a meal), and suppression of food ingestion, underling mechanisms play a vital role in these decreased levels. The serum ghrelin levels will vary as energy balances. Levels will increase in cases of anorexia, and decrease in obesity cases. What this tells us is that ghrelin levels might be important as it pertains to food intake and consumption. Both in over and under-eating cases, ghrelin can have a dual-effect, signaling hunger in the somatotopic axis. This can also play an integral role in balance and energy levels.

The effects on Obesity: GHRP-6

As a leader in the synthetic peptide family, GHRP-6 enhances release of GH hormone in the pituitary gland. This is done in a dose dependent manner. After its discovery, it’s been a leading benchmark for a number of research studies to obtaining new drugs. But, the greatest implication has come in the treating of obesity and the epidemic in the US. Whether spontaneous or evoked, the normal GH secretion is blunted in patients who are obese. This is in comparison to normal-weight individuals. Scacchi (et el) found that when GHRH and GHRP-6 were administered simultaneously, the most powerful GH release occurred. This was still less effective in comparison to the normal-body weight counterpart.

A conclusion to treat with biosynthetic GH has proven to help with body composition in such subjects. Metabolic efficacy is also attainable with therapeutic, and severe caloric restriction. What this concludes is that GHRP can help in obesity therapies, and aiding patients in weight loss.

Another study which was used to determine effects of estrogen and GHRP-6 was conducted on rats. This was to determine metabolic diseases and cardiovascular effects in OVX rats. Elbassuoni, et el, found this study failed in producing a change (weight gain or loss). It also reversed the effect of OVX in insulin, insulin resistance levels, and lipid fractions.

The conclusion was that GHRP-6 improved dyslipidemia after OVX was far more potent than the estrogen administration was. The mechanism of GHRP-6 has also been extensively studied in various models using obese subjects. It was proven to have a great impact on GH releaser, and released GH independently of hypothalamic factors.

 

What exactly is Ghrelin?

The scientific definition is the 28-amin acid hunger simulating peptide. It is a hormone which is produced by D1/P cells, which line the fundus of the stomach. It also lines the epsilon cells in the pancreas. When working with obestatin, ghrelin is produced from cleavage of the prepropeptide. This in turn is encoded by GHRL genes. These receptors are expressed in various tissue functions, to include the pituitary, the stomach, pancreas, the intestine, gonads, heart, the thyroid, and the thymus. Ghrelin receptor locations also suggest it has a great impact on the biological functions our bodies undergo routinely.

How does Ghrelin work?

Prior to meals the levels increase, and following a meal they decrease. Many consider it the counterpart to the leptin hormone, which is produced by adipose tissue. This helps induce satiation levels. During bariatric procedures, ghrelin levels are reduced, which helps decrease satiation levels, which were previously present in the patients. Ghrelin is a highly potent stimulating GH hormone. The secretion from the anterior pituitary gland, when coupled with the G protein receptor, is known as secretagogue receptor. Basically, ghrelin will bind to GHSR1 (which is a splice variant), and is highly dense in the hypothalamus, the pituitary, and vagal afferent cell bodies. These align the GI-tract.

Ghrelin has often been linked to helping induce one’s appetite and their feeding patterns. The circulating levels are highest right before a meal, and conversely lowest, after a meal. Ghrelin injections in humans (and rats) have shown increases in food intake, which occur in dose-dependent manners. This means, more ghrelin, higher food consumption in humans. Ghrelin doesn’t increase meal size, only frequency.  The injections are also known to increase in an animal’s motivation to hunt/seek out food. This includes: foraging, sniffing, and food-hoarding.

Ghrelin also aids in helping the body prepare for incoming nutrients. This is achieved by stimulating motility in the gastrointestinal system. It is also accomplished by gastric acid secretions which occur naturally in the body.