The following structure is taken from, Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults, Sam L. Teichman, Ann Neale, Betty Lawrence, Catherine Gagnon, Jean-Paul Castaigne, and Lawrence A. Frohman, J Clin Endocrinol Metab, March 2006, 91(3):799–805
NOTE that native GRF(1-29) is native GHRH or GRF(1–44) with the inactive final 15 amino acids removed.
It is very important to use ONLY modified GRF(1-29) w/ the four amino acid substitutions as discussed before and NOT unmodified GRF(1-29)
Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences, Robert M. Campbell,Peptides Volume 15, Issue 3, 1994, Pages 489-495
Native human GRF(1–44)-NH2 (hGRF44) is subject to biological inactivation by both enzymatic and chemical routes. In plasma, hGRF44 is rapidly degraded via dipeptidylpeptidase IV (DPP-IV) cleavage between residues Ala [at the 2nd position] and Asp [at the 3rd position]. The hGRF44 is also subject to chemical rearrangement [at the 8th position] and oxidation [at the 27th position] in aqueous environments, greatly reducing its bioactivity.
It is therefore advantageous to develop long-acting GRF analogues using specific amino acid replacements at the amino-terminus [2nd position] (to prevent enzymatic degradation): residue 8 (to reduce isomerization) and residue 27 (to prevent oxidation). Inclusion of Ala [at the 15th position] substitution for Gly, previously demonstrated to enhance receptor binding affinity, would be predicted to improve GRF analogue potency.
In vitro, these analogues were approximately threefold more potent than hGRF44, whereas in vivo they were eleven- to thirteenfold more potent. As the in vitro results reflect only receptor affinity and signal transduction, the increment in potency observed in vivo is likely due to the increased biological half-life of these analogues (i.e., the result of decreased enzymatic and chemical decomposition such that more bioactive peptide is available per unit time).
So these changes are made to reduce enzymatic cleavage, amino rearrangement and oxidation in plasma.
In addition "Ala [position] 15-substitution (for Gly) displayed 4–5 times higher affinity for the GRF receptor relative to hGRF(1–44)-NH2...and hence potency." - GRF analogs and fragments: Correlation between receptor binding, activity and structure, Robert M. Campbel, Peptides Volume 12, Issue 3, May-June 1991, Pages 569-574
So the above highlighted amino acids need to be modified to:
2nd position - D-Ala
8th position - Gln
15th position - Ala
27th position - Leu
What effect can substituting D-Ala for Ala at the 2nd amino acid position on GRF(1-29) have on total growth hormone release?
"...While trypsin-like degradation of GHRH also occurs, in vitro studies using GHRH analogs designed to resist cleavage at the N-terminus have demonstrated that the primary degradation of GHRH is via DPP-IV. Substitution of Ala2 with DAla prevents DPP-IV proteolysis, and administration of this analog increases GH release in swine up to 2-fold (7)." - Inhibition of Dipeptidyl-Peptidase IV Does Not Increase Circulating IGF-1 Concentrations in Growing Pigs, T. D. Faidley, Experimental Biology and Medicine 231:1373-1378 (2006)
Reference:
7 - Rational design, synthesis, and biological evaluation of novel growth hormone releasing factor analogues, Campbell RM, Bongers J, Felix AM,Biopolymers 37:67–88, 1995
Thats correct. Sermorelin is a precription drug composed of the first 29 amino acids of GHRH. No alterations have been made to increase stability or potency.
Thats correct. Sermorelin is a precription drug composed of the first 29 amino acids of GHRH. No alterations have been made to increase stability or potency.
For curiosity sake, here is a 6 month study for sermorelin (unaltered GRF 1-29) that showed a 30% increase in IGF-1 levels of a normal aging male from only one nightly sub q inject. (23% for women not taking E2 replacement).
Not sure of the dosage as the full study is "pay per"...
I'll add that sermorelin was never adopted by the mainstream for children with short stature because it could not sufficiently raise levels adequetly.
In AGHD it was far from providing optimal results in most cases unless multiple daily injections were performed (no doubt about that).
Obviously the evolutionary trend was the creation of analogs with substitutions and biocunjugation...
For curiosity sake, here is a 6 month study for sermorelin (unaltered GRF 1-29) that showed a 30% increase in IGF-1 levels of a normal aging male from only one nightly sub q inject. (23% for women not taking E2 replacement).
Not sure of the dosage as the full study is "pay per"...
I'll add that sermorelin was never adopted by the mainstream for children with short stature because it could not sufficiently raise levels adequetly.
In AGHD it was far from providing optimal results in most cases unless multiple daily injections were performed (no doubt about that).
Obviously the evolutionary trend was the creation of analogs with substitutions and biocunjugation...
Dat if someone had sermorelin would it not be a better idea to inject it into something like the traps? Sounds like a weird idea, but would this not be the closest injection site to the anterior pituitary or would we have to study the circulatory system (now that I think about it, the veins in the traps might go to the heart or around the body before hitting the brain).
Just an update, 2mg of cjc per week is far far far better than the 1.2mg I was using with ghrp6. Shots before were done pwo and before bed at 100mcg cjc+200mcg ghrp6 6days per week. Recently I switched it to 150mcg cjc+200mcg ghrp6 same 2x per day, everyday and results got much better(non training days pwo shot is replaced with morning shot). Ever since Dat thought I was using the GFR i split my shots into 3 per day to get more outta the GFR(if thats even what im using, who's knows with china) but I havent noticed much more since doing this but its only been a week. But i wanted to say that the 2mg mark is where the cjc should be. I still dont think this protcol can compare to high doses of gh like 8-10iu's per day, but im definately staying much leaner while under lots of stess and a poor diet. I would compare this to around 4-5iu's GH everday which is great in my opinion.
Yes, an upstream arterial inject is the shortest distance to the point of interest.
However, site injects (IM or Sub Q) are tissue injects that will make it into the capillaries and return to the heart via venous blood, unless injected directly into a particular vessel.
Yes, an upstream arterial inject is the shortest distance to the point of interest.
However, site injects (IM or Sub Q) are tissue injects that will make it into the capillaries and return to the heart via venous blood, unless injected directly into a particular vessel.
Dat re. the discussion a page back concerning the benefits of GRF (1-29) vs CJC no-one mentioned dosage of the former. If an optimal or maximum practical dosage of CJC is 2.1mg/week for bbing or whatever, what about GRF? Since, that is, the Chinese supplier I got my "CJC" from acknowledges upon inquiry that it is indeed GRF and I don't seem to be pining CJC after all. And golly I admit I regret having to pin 3 times per day to get the same results. Does it make any sense whatsoever to combine the two with GHRP 6? Thanks as always.
Dat re. the discussion a page back concerning the benefits of GRF (1-29) vs CJC no-one mentioned dosage of the former. If an optimal or maximum practical dosage of CJC is 2.1mg/week for bbing or whatever, what about GRF? Since, that is, the Chinese supplier I got my "CJC" from acknowledges upon inquiry that it is indeed GRF and I don't seem to be pining CJC after all. And golly I admit I regret having to pin 3 times per day to get the same results. Does it make any sense whatsoever to combine the two with GHRP 6? Thanks as always.
Everything I've ever discussed concerning my prefered dosing protocol is based on what is well established in the studies. In addition I always treated CJC-1295 as if it were just GHRH (Growth Hormone Releasing Hormone).
Keep in mind that EVERYTIME we talk about CJC-1295, EVERYTIME we talk about modified GRF(1-29) and EVERYTIME we talk about GRF(1-29) or Sermorelin we are referring to GHRH.
It is all GHRH.
There is a huge problem with just dosing GHRH. The problem is that the GH response illicited is variable & not precisely predictable. Even within the same person there can be as much as 60% variablity depending on when they take it.
GHRH administered in a GH trough results in low amounts of GH release while GHRH administered during a rising natural GH pulse will result in high amounts of GH release. See:
The Interaction Between Clonidine And Growth Hormone Releasing Hormone
In The Stimulation Of Growth Hormone Secretion In Man, D. Suri, Clinical Endocrinology (1990), 33, 399-406
But what about GHRP-6 by itself? Well yes it does instigate a reliable GH pulse BUT most of its action requires the presence of GHRH (either natural or exogenic). See:
Growth Hormone (GH)-Releasing Peptide-6 Requires Endogenous Hypothalamic GH-Releasing Hormone for Maximal GH Stimulation, NAUSHIRA PANDYA, ROBERTA DEMOTT-FRIBERG, CYRIL Y. BOWERS, ARIEL L. BARKAN, AND CRAIG A. JAFFE, Journal of Clinical Endocrinology and Metabolism 1998 Vol. 83, No. 4
The large pulse is a result of exogenic GHRP-6 administration w/ the body making its own GHRH.
The small pulse is a result of exogenic GHRP-6 administration w/ the supression of the body's ability to make its own GHRH.
So GHRP-6 works fine if the body makes GHRH. From plenty of other studies we know that it works even better if coadministered with exogenic administration of GHRH.
Now I am only going to reiterate the point I have made many times and explained in detail elsewhere including my original articles -
GHRH at saturation dose is synergistic with low dose or saturation dose of GHRPs (Growth Hormone Releasing Peptides) of which GHRP-6 is one
GHRPs are capable of creating a pulse no matter what the current state of endogenic GHRH/Somatostatin. They do so in part by reducing somatostatin's influence at the pituitary and decreasing its release at the hypothalamus. *
So to directly answer your question YES it makes since to dose GHRH & GHRP-6 together. It does not make since to dose GHRH (in whatever form) by itself.
* - NOTE: for a more detailed explanation see my original articles posted on page one of this thread.
Dat whats your thoughts on not eating for an hour before and after administering your daily gh injection. Myth? (Yes im sure this topic has been covered on this site, couldnt find it, if anyone has a link lemme know)
Thanks dat. Heres one more for ya. What r your thoughts on long cytomel cycles? I planned on doing 2 months but probably will extend that to 3. I also upped the dosage from .25 to .5.
If you are asking me what I think of T3 use in general...well for myself I have no worries that I could use it for several months and come off and recover fine. I've done it before.
For me personally though whether I use it for a couple of weeks or a couple of months I always have a period of time where it takes a week and a half to get my metabolism back to "normal". During that time I get some fat rebound...in part because you need carbs to help get things back to normal. Obviously less rebound if I up the cardio... so I don't really use it.
Getting away from my own experience and speaking generally the administration of T3 appears to be a lot safer then Clenbuterol.
.gif "IP Gear")
