GHRP-2 is basically a synthetic-version of Ghrelin analogue. It helps stimulate release of the GH (endogenous growth hormone) within somatotropins found in the anterior pituitary gland, both in humans and animals.
Specifically, GHRP-2 helps increase the amount of somatotropins in the GH pulse by limiting somatostatin. Further, the standard GHRH increases the amplitude where the pituitary cells pulse. GHRP-2, unlike ghrelin, isn’t used to increase the appetite, but may be a secondary reaction which occurs. Effects will last approximately 1-hour upon application, and can last up to an 8-hour circulation period.
1973, 1976, 1982 and 1984, 1990, 1996, 1998, and 1999, mark historical points in the development of the enlarging ghrelin system. During this period, these events occurred sequentially:
The discovery of GH secretagogin GHS/GHRP receptor cloning of the receptor isolation, and the identification of new, natural, endogenous GHRP ghrelin. This discovery was the result of countless hours, and numerous studies which were conducted for many years, by dedicated, talented researchers and scientist.
The dedication of many, talented researchers from around the world, led to our contemporary understanding of the pharmacology (and physiological regulation of growth hormone secretion), came about after an important discovery was made. This discover that GHRP increased pulsatile (GH) secretion not only in children, but also younger and older men and women, marked a major breakthrough in science.
GHRP alone releases GH from the pituitary in-vitro, in substantial levels. This is done without the addition of GHRH. It was discovered that the rhythmic, endogenous secretion doesn’t require GHRH to be present. Initially, GHRP was envisioned as an analog form of GHRH. However, upon comparison of the internal activities of both GHRH and GHRP (from 1982-1984), hypothesis surfaced reflecting activity outside the new hormone regulator (GH) was an isolated incident.
IV-bolus GHRP releases a greater amount of GH than GHRH in humans. However, when released in-vitro, the reverse occurs. Lower levels are released in the system when IV is used to administer the hormones. The GHRP acts like pleiotropic-peptides, having a great effect on GH hormones. Further, a positive effect is noted on the metabolism (by helping increase the rate at which the metabolism works), overall nutrition levels (increased appetite, healthier foods, etc.), and especially in working as an additional hormone alongside GHRH (as the new regulator pulsatile of GH secretion). All of these positive benefits lead to increased health in users of the hormone overtime.
A major increase of food intake was noticed in test subjects who were given GHRP. This was basically the first indication of pleiotropism being present. The similar (yet different and complementary) action with GHRH on GH regulation and secretion, has been a leading factor as to why there has been a prolonged interest in GHRPs as they work within the human-organisms. They can counter-balance negative dietary practices in those who are using the hormone injections over a prolonged period of use.
Of particular importance is the variable chemistry of GHRP, and the benefits it affords to those who are using it. Basically, GHRP is made up of 3-major chemical classes. The chemical-classes are: peptides, partial-peptides, and non-peptides. The same receptor and cellular mechanisms affect these peptide-bonds.
It is also of high importance to note that most GHRP has been active through various administration routes. Most notably it is administered through IV and SC as the leading delivery mechanisms of GHRP. However, it is has also administered via intranasally and IVC (intracerebroventricularly) in a number of patients and test subjects (human and animal) over the years. This helps support the potential broad future clinical utility use in the future, and also allows for different dosage amounts when administering the GHRP through different methods.
Numerous evolutionary studies have been conducted, which began with the zebrafish. In these studies, we’ve learned that natural receptors and hormones have been present for several hundreds of years. This has showcased the fundamental evolutionary and functional importance of the ghrelin system. It has been well established that GHRP was intended to act directly on the pituitary and hypothalamus glands, several years prior to the GHS receptor assay.
A final note on this subject is in relation to the ghrelin chemical isolation and identification. Both were accomplished in the stomach, which was the major, but not the only, site of production. Ghrelin was identified and isolated in these studies.
GHRP continues to be of major concern in relation to GH secretion and regulation. However, direct and indirect effects on nutrition and the metabolism have also been linked to GHRP. A variety of other actions which maybe physiological and pharmacological, have also been linked to GHRP secretion in the human system.
So, now that we’ve identified what GHRP does in the system, you might be wondering if GHRP-2 works. In the studies presented below, we will see the actions of both GHRP-2 and GHRP-6 on GH releases which occur in pituitary cells. The follow-up study focused on increasing the concentration levels of both GHRP-2 and GHRP-6, in an attempt to create a higher GH-dependency, to help identify potential dosing restrictions.
Should the chemical be used in therapeutic sessions in the future? The studies indicated that GHRP-2, GHRP-6, and GRF, were applied increasingly to partially purified sheed somatrophs. This was done to cause the release of GH in a dependent manner. Although GHRP-6 levels didn’t increase cAMP levels, mixtures of GRHP-2 and GRP did increase the growth hormone and cAMP levels. The study further showcased that combinations of GHRP-2 and GHRP-6 didn’t increase these levels.
Adenylyl cyclase inhibitor was used to penetrate the cells. In these incidents, an increase in cAMP levels didn’t occur. A GH increase when GHRP-2 or GRF were applied did result in increased levels.
Basically, the studies indicated how the antagonist didn’t prevent cAMP increase reactions in incidents where a combination of GH and GHRP-6 were applied. Conversely, when the antagonist was applied to GH receptors, GRF and GHRP-2 combinations didn’t increase cAMP rates. Rather, this prevented release of GH, when GHRP-2, GHRP-6, or GRF was applied.
In studies, GHRP-2 has demonstrated the ability to affect the ovine pituitary somatotroph which conversely increased cAMP concentrations similarly to GRF. On the other end of the spectrum lies the fact that GHRP-2, GRF, and GHRP-6 will act differently on the receptors. This helps explain why GHRP-6 didn’t affect cAMP levels on rat cell cultures.
Numerous studies and research has shown that circulating ghrelin is an implication in meal-to-meal regulation. The levels increase in anticipation of an upcoming meal, and are later suppressed by food ingestion. The underlying mechanisms aren’t known in these research studies.
For energy balance to occur, serum ghrelin levels vary. In cases of anorexia they are increased, and cases of obesity the ghrelin levels are lower/decreased. What this shows it that ghrelin levels might be a relatively important factor in food intake behaviors. And, it might also be a chronic condition, for over or under-nutrition levels.
As ghrelin has dual-effects on the body, it may be a critical hormonal signal of nutritional status. This goes through the somatotropic axis, and plays an integral role in energy balance, and in the growth process.
Numerous studies have shown that the peripheral administration of GHRP-2, has the adverse effect of increased food intake in humans. GHRP-2 effects are robust, and did indicate a food intake increase on all test subjects to which it was administered. All of the subjects reported to being hungrier when receiving GHRP-2.
A great increase in food take was shown in subjects who were ingesting the GHRP-2, by a 35% increased, which was comparable to that of ghrelin, which conversely showed an increase of 28% in healthy subjects, and 31% in cancer-patients who underwent the study.
The studies further indicated that the effect of 1 g/kg/h of GHRP-2 was comparable to the effects of ghrelin (given at 5 pmol/kg/min). The increase was noted not only in food intake levels, but also in the release of the GH hormone.
Wren’s study was conducted on healthy, lean-subjects, showed an increase in the ghrelin levels which raised GH release (at about 35 g/L). What this showed was that ghrelin (or ghrelin mimetic GHRP-2), when it was administered peripherally, is capable of inducing changes. These changes are acute in scope, similar in magnitude in GH level and food intake behaviors.
Chronic administration of GHRP-2 to short-stature children (with various GH deficiencies) induced a sustained enhancement in linear growth. This was noted in various studies which were conducted in children.
What these studies suggest is the possibility of an acute effect of GHRP-2 on food intake. This was namely observed in studies proving a positive energy balance, where GHRP-2 was administered chronically. Numerous studies which were careful designed (and optimized), including the detailed body composition and food intake monitoring, help demonstrate longer-term effects of GHS on food. They also have an effect on body weight of test subjects.
Studies indicate that GHRP-2 increased GH levels significantly. From studying these results, it is therefore unlikely that rhGH on its own, would increase the GH levels significantly. Therefore, it is only responsible for the acute changes in food intake, not in GH production.
As with the above, studies were conducted to determine the effects of GHRP-2 on inflammation levels. One such study focused on the administration of GHRP-2 on arthritic rats. When injected with Freunds adjuvant, and exposed daily to GHRp-2 (or ghrelin) 15 days later, numerous, interesting results were presented.
First off, the study showcased how those rates which were exposed to the ghrelin serum, saw a noticeable decrease in lepin concentrations. Conversely, the rates who were given GHRP-2 realized ameliorated external symptoms. This was due to their arthritic condition, and a decrease in paw-volume was also noted in these subjects.
In rats who had the GHRP-2 administered, a noted decrease in IL-6 levels was found. This was after the levels were originally increased by the symptoms stemming from their arthritis.
So, what exactly can we take from the studies and the results which were presented? Basically, the results help in showing how GHRP-2 may be used in managing IL-6 levels. This is of course in the cases of patients (test rats) which were affected by arthritis.
Another implication we can draw is that GHRP-2 may have anti-inflammatory benefits. The anti-inflammatory properties, have a positive effect on managing ghrelin receptors. Further, immune cells which were affected by the disease are also better managed when GHRP-2 is administered.
When comparing GHRP-2 to similar chemicals found in natural settings, researchers can glean many benefits. This form of testing is an ongoing process researchers can use. They can use such research and studies to evaluate similarities in body composition. Further, the studies of the GHRP-2 chemical can be expanded on other animals. This can help better determine how it might affect humans, who have similar composition, and similar conditions.
Of course, the studies and research which was conducted on rats, is only a means to glean the benefits of GHRP-2 and the release of the GH hormone. With this being said, there are numerous benefits, which can be linked to humans, who are also administering GHRP-w through IV therapy or SC.
Depending on the level/amount being administered, a number of benefits might present themselves. These can range from decreased inflammation in arthritic patients, or an increase in appetite for those who suffer from anorexia.
Although the results are not going to mimic identically the effects on the rat test subjects, researchers can continually learn how the GHRP-2 will affect users. For such reasons, it is beneficial to understand how GHRP-2 works, the reaction GHRP-6 might cause on certain users, and how this works with the release of the GH hormone in humans who are using these injections to treat various conditions.