Strength: 3mg/3mg

Size: 1 Kit

GHRH (Sermorelin) and GHRPs Overview

Growth Hormone

Synthetic Growth Hormone is an artificially created hormone “identical” to the major naturally produced (endogenous) isoform. It is often referred to by its molecular mass which is 22kDa (kilodaltons) and is made up of a sequence of 191 amino acids (primary structure) with a very specific folding pattern that comprise a three-dimensional structure (tertiary structure). This tertiary structure is subject to potential shape change through a process known as thermal denaturation. While many labs are capable of generating growth hormone (GH) with the proper primary structure not all will be capable of creating a tertiary structure identical to the major naturally occurring growth hormone. The tertiary structure can determine the strength with which the growth hormone molecule binds to a receptor which will in turn affect the “strength” of the intracellular signaling which mediates the events leading to protein transcription, metabolism, IGF-1 creation, etc. It is this inconsistency that accounts in part for the differences in effectiveness of various non-pharmaceutically produced synthetic growth hormone.

Naturally produced Growth Hormone is produced in the anterior pituitary and to a far lesser extent in peripheral tissue. It is made up of a blend of isoforms the majority of which is the 22kDa (191 amino acid) variety with which most are familiar. In addition an isoform that is missing the 15 amino acids that interact with the prolactin receptor is also produced. This form is known as 20kDa and although it binds differently to the growth hormone receptor it has been shown to be equally potent to 22kDa. It appears that 20kDa has lower diabetogenic activity then 22kDa. The pituitary releases a blend of these two isoforms with 20kDa averaging perhaps 10% of the total although this percentage increases post-exercise. Currently there is no synthetic produced for external administration for this isoform.

Growth hormone (GH) in the body is released in pulsatile fashion. It has been demonstrated that this pattern promotes growth. The pituitary is capable of rather quickly synthesizing very large amounts of growth hormone which it stores large amounts in both a finished and unfinished form. Adults rarely experience GH pulses (i.e. releases of pituitary stores) that completely deplete these stores. As we age we do not lose the ability to create and store large amounts of growth hormone. Rather we experience a diminished capacity to “instruct” their release. The volume of GH that is released can not be properly equated to the exogenous administration of synthetic GH for the reason that a set of behavioral characteristics accompany natural GH that differ from those of synthetic GH. Among those characteristics are concentrated pulsatile release which upon binding in mass to growth hormone receptors on the surface of cells initiate signaling cascades which mediate growth events by translocating signaling proteins to the nucleus of the cell where protein transcription and metabolic events occur.

These very important signaling pathways desensitize to Growth Hormone’s initiating effects and need to experience an absence of Growth Hormone in order to reset and be ready to act again. The presence of GH released in pulsatile fashion is graphed as a wave with the low or no growth hormone period graphed as a trough. Therefore attempting to find a natural GH to synthetic GH equivalency

is not very productive because in the end what is probably import is:

• the quantity & quality of intracellular signaling events; and
• the degree to which GH stimulates autocrine/paracrine (locally produced/locally used) muscle IGF-1 & post-exercise its splice variant

Brief overview of natural GH release:

The initiation of growth hormone release in the pituitary is dependent on a trilogy of hormones:

Somatostatin which is the inhibitory hormone and responsible in large part for the creation of pulsation; Growth Hormone Releasing Hormone (GHRH) which is the stimulatory hormone responsible for initiating GH release; and Ghrelin which is a modulating hormone and in essence optimizes the balance between the “on” hormone & the “off” hormone. Synthetic growth hormone releasing peptides (GHRPs) were created and are superior to Ghrelin in that they do not share Ghrelin’s lipogenic behavior. These GHRPs are GHRP-6, GHRP-2, both behave in similar fashion. In the aging adult these Ghrelin-mimetics or the GHRPs restore a more youthful ability to release GH from the pituitary as they turn down somatostatin’s negative influence which becomes stronger as we age and turn up growth hormone releasing hormone’s influence which becomes weaker as we age.

The exogenous administration of Growth Hormone Releasing Hormone (GHRH) creates a pulse of GH release which will be small if administered during a natural GH trough and higher if administered during a rising natural GH wave.

Growth Hormone Releasing Peptides (GHRP-6, GHRP-2) are capable of creating a larger pulse of GH on their own then GHRH and they do this with much more consistency and predictability without regard to whether a natural wave or trough of GH is currently taking place.

Synergy of GHRH + GHRP

Growth Hormone Releasing Hormone (GHRH) however is currently available in several forms which vary only by their half-lives. Naturally occurring GHRH is either a 40 or 44 amino acid peptide with the  bioactive portion residing in the first 29 amino acids. This shortened peptide identical in behavior and half- life to that of GHRH is called Growth Hormone Releasing Factor and is abbreviated as GRF(1-29).

GRF(1-29) is produced and sold as a drug called Sermorelin. It has a short-half life measured in minutes.

While the GHRPs (GHRP-6, GHRP-2) come in only one half-life form and are capable of generating a GH pulse that lasts a couple of hours re-administration of a GHRP is required to effect additional pulses.

It is well documented and established that the concurrent administration of Growth Hormone Releasing Hormone (GHRH) and a Growth Hormone Releasing Peptide (GHRP-6, GHRP-2 or Hexarelin) results in synergistic release of GH from pituitary stores. In other words if GHRH contributes a GH amount quantified as the number 2 and GHRPs contributed a GH amount quantified as the number 4 the total GH release is not additive (i.e. 2 + 4 = 6). Rather the whole is greater than the sum of the parts such that 2 + 4 = 10.

A Brief Summary of Dosing and Administration of GHRH (Sermorelin) and GHRPs

Dosing GHRPs:

The saturation dose in most studies on the GHRPs (GHRP-6, GHRP-2) is defined as either 100mcg or 1mcg/kg.  What that means is that 100mcg will saturate the receptors fully, but if you add another 100mcg to that dose only 50% of that portion will be effective. If you add an additional 100mcg to that dose only about 25% will be effective. Perhaps a final 100mcg might add a little something to GH release but that is it.

So 100mcg is the saturation dose and you could add more up to 300 to 400mcg and get a little more effect. A 500mcg dose will not be more effective then a 400mcg, perhaps not even more effective then 300mcg. The additional problems are desensitization & cortisol/prolactin side-effects.

GHRP-6 at the saturation dose 100mcg does not really increase prolactin & cortisol but may do so slightly at higher doses. This rise is still within the normal range.

GHRP-2 is a little more efficacious then GHRP-6 at causing GH release but at the saturation dose or higher may produce a slight to moderate increase in prolactin & cortisol. This rise is still within the normal range although doses of 200 – 400mcg might make it the high end of the normal range.

Desensitization

GHRP-6 can be used at saturation dose (100mcg) three or four times a day without risk of desensitization.  GHRP-2 probably at saturation dose several times a day will not result in desensitization.  Chronic use of GHRP-6 at 100mcg dosed several times a day every day will not cause pituitary problems, nor significant prolactin or cortisol problems, nor desensitize.

GHRH – Sermorelin

Sermorelin, GHRH (1-44) and GRF(1-29) all are GHRH and have a short half-life in plasma because of quick cleavage between the 2nd & 3rd amino acid. This is not of much concern because this hormone is secreted from the hypothalamus and travels a short distance to the underlying anterior pituitary and is not really subject to enzymatic cleavage. The release from the hypothalamus and binding to somatotrophs (pituitary cells) happens quickly.  However when injected into the body it must circulate before finding its way to the pituitary and so within 3 minutes it is already being degraded.  That is why GHRH in the above forms must be dosed high to get an effect.

Problem With Using any GHRH (Sermorelin) alone

The problem with using a GHRH even the stronger analogs is that they are only highly effective when somatostatin is low (the GH inhibiting hormone). So if you unluckily administer in a trough (or when a GH pulse is not naturally occurring) you will add very little GH release. If however you luckily administer during a rising wave or GH pulse (somatostatin will not be active at this point) you will add to GH release.

Solution is GHRP + GHRH analog

The solution is simple and highly effective. You administer a GHRH analog with a GHRP. The GHRP creates a pulse of GH. It does this through several mechanisms. One mechanism is the reduction of somatostatin release from the hypothalamus, another is a reduction of somatostatin influence at the pituitary, still another is increased release of GHRH from the brain and finally GHRPs act on the same pituitary cells (somatotrophs) as do GHRHs but use a different mechanism to increase cAMP formation which will further cause GH release from somatotroph stores. GHRH also has a way of reciprocally reinforcing GHRPs action.  The result is a synergistic GH release. The GH is not additive it is synergistic.

For example If GHRH by itself will cause a GH release valued at 2

and GHRP itself will cause a GH release valued at 5, together the GH is not 7 (5+2) it turns out to say 14.

Protocols

A well established protocol would be to use a GHRP + a GHRH analog pre-bed (to support the nightime pulse) and once or twice throughout the day. For anti-aging, deep restful restorative sleep, the once at night dosing is all you need. For an adult aged 40+ it is enough to restore GH to youthful levels. However for fat loss or injury repair multiple dosing can be effective. The GHRH analog can be used at 100mcg and as high as you want without problems. The GHRP-6 can always be used at 100mcg w/o problems but a dose of 200mcg will probably be fine as well.

Again desensitization is something to keep an eye on particularly with the highest doses of GHRP-2.

So 100 – 200mcg of GHRP-6 + 100 – 500mcg+ of a GHRH (Sermorelin) taken together will be effective. This may be dosed several times a day to be highly effective.

A solid approach is a bit more conservative at 100mcg of GHRP-6 + 100mcg of a GHRH analog dosed either once, twice, three or four times a day. When dosing multiple times a day at least 3 hours should separate the administrations.

The difference is once a day dosing pre-bed will give a youthful restorative amount of GH while multiple dosing and or higher levels will give higher GH & IGF-1 levels when coupled with diet & exercise will lead to muscle gain & fat loss.

Dose without food

Administration should ideally be done on either an empty stomach or with only protein in the stomach. Fats & carbs blunt GH release which is also another reason not to snack before going to bed. So administer the peptides and wait about 20 minutes (no more then 30 but no less then 15 minutes) to eat. AT that point the GH pulse has about hit the peak and you can eat what you want.