Dat's - CJC-1295 & GHRP-6 (Basic Guides)

Dat-
Do you remember exactly where we were discussing concurrent administration of GHRH/GHRP and exo GH> I beleieve the theory was multiple dosing of each, but I don't remember particulars.

In response to the PMs asking for a basic primer so that they can understand this thread I offer the beginning of a series...What is a peptide?

Peptides (proteins) are present in every living cell and possess a variety of biochemical activities. Some peptides are synthesized in the ribosomes of a cell by translation of mRNA (messenger RNA) into hormones and signaling molecules for example. Other peptides are assembled (rather then synthesized) and become enzymes with a vast variety of functions. Peptides also make up the structure of receptors which await binding of hormones & signaling molecules.

A peptide is a molecule created by joining two or more amino acids. In general if the number of amino acids is less than fifty, these molecules are called peptides, while larger sequences are referred to as proteins.

So peptides can be thought of as tiny proteins. They are merely strings of amino acids.

Raw Constituents of Peptides (Amino Acids)

Amino acids are small molecules made up of atoms. As part of their structure they posses a grouping of a Nitrogen (N) atom bonded to two Hydrogen (H) atoms. This is called an amino group and written as (NH2). In addition their structure is also made up of a second grouping of a Carbon (C) atom bonded to two Oxygen (O) and one Hydrogen atom. This group is called a carboxyl group and is written as (COOH).


Between these two groupings are atoms and bonds unique to each amino acid. In other words all amino acids possess the two groupings (amino & carboxyl) as end-points between which are sandwiched a unique set of atoms.

Amino Acids

Inside the human body there are twenty standard amino acids used by cells in peptide biosynthesis (i.e. the cellular creation of peptides from amino acids). Our genetic code specifies how to synthesize peptides and proteins from these amino acids.

Amino acids are classified into two groups: essential amino acids and nonessential amino acids.

An essential amino acid is an indispensable amino acid which cannot be made by the body and must be supplied by food. These include isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Another amino acid - histidine is considered semi-essential because the body does not always require dietary sources of it.

Nonessential amino acids are made by the body from the essential amino acids or the routine breakdown of proteins. The nonessential amino acids are arginine, alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine.

All twenty amino acids are equally important in maintaining a healthy body. They are the raw constituents of peptides and proteins.

The standard abbreviations for amino acids come in two forms: a one letter form and a three letter form. They are:

A - Ala - Alanine
C - Cys - Cysteine
D - Asp - Aspartic Acid
E - Glu - Glutamic Acid
F - Phe - Phenylalanine
G - Gly - Glycine
H - His - Histidine
I - Ile - Isoleucine
K - Lys - Lysine
L - Leu - Leucine
M - Met - Methionine
N - Asn - Asparagine
P - Pro - Proline
Q - Gln - Glutamine
R - Arg - Arginine
S - Ser - Serine
T - Thr - Threonine
V - Val - Valine
W - Trp - Tryptophan
Y - Tyr - Tyrosine


Amino acids exist in either D (dextro) or L (levo) form. Most of the amino acids found in nature (and all within human cells) are of the L-form. As a generality all amino acids except glycine have a mirror image of the L-form. This mirror image is called the D-form. It is common when referring to the L-form (naturally occuring form) to leave off the "L" designation whereas the "D" designation is always explicitly written.

D-amino acids are found naturally in bacterial cell walls and used in some synthetic peptides to make a peptide more stable or more resistant to degradation.

Amino Acid + Amino Acid = Peptide

The amino acids are joined together by what is known as a "peptide bond". A "peptide bond" is a linkage in which the nitrogen atom of one amino acid (from the amino group (NH2) binds to the carbon atom of another amino acid's carboxyl group (COOH).

During this binding process a molecule of water is released. This is called a condensation reaction.

The resulting CO-NH bond is called a peptide bond, and the resulting molecule is called an amide.

On the following image note that the COOH group gives up an Oxygen Hydrogen (OH) bond and the NH2 group gives up a Hydrogen (H). This forms H2O, which is a water molecule which is not part of the newly created peptide. NOTE: in the following image the C (carbon) symbol is missing as it is assumed so I indicate it with a blue square.


This reaction creating a peptide bond between two amino acids creates a peptide. We can call this peptide (made up of two amino acids) a dipeptide.

This process can be repeated using the twenty amino acids as raw material to create longer peptide chains. Sometimes peptide chains consisting of fifty to 100 amino acids are called polypeptides. Often a peptide chain beyond 100 amino acids is called a protein.

GHRP-6 is a peptide made up of just six amino acids. It's structure is often written as His-DTrp-Ala-Trp-DPhe-Lys-NH2

Note that the Carboxyl grouping (COOH) is assumed in the first position and is usually not written. The amino group (NH2) is wrtitten in the last position. The "meat" or the part that makes GHRP-6 distinct is the seqence in the middle of histadine bonded to the "D" form of Tryptophan bonded to Alanine bonded to Tryptophan bonded to the "D" form of Phenylalanine bonded to Lysine.

Pepdide bonds are formed by water (H2O) condensation (removing water). The converse is also true. A peptide bond can be broken down by hydrolysis (adding water).

...

[To be continued]

Administering IGF-1 does not work

Anyone who is familiar with what I write will know that I have really tried to avoid making a blanket statement on the ineffectiveness of administering IGF-1. I even discussed the possibility of making it work to some degree by prebinding it to IGFBP-3. Whenever I get close to saying that IGF-1 is ineffective though I seem to get some very emotional reactions.

I have held the position that circulating levels of IGF-1 derived from the liver are not relevant for growth. It is the little bit of IGF-1 that is created in muscle & used there that is important.

To effect this I have pointed out that GH & to some extent testosterone effect this autocrine/paracrine action (i.e. locally made & used both within a cell and neighboring cells).

Here is a very good summary of what GH does & what IGF-1 does not do.

CONTROL OF GROWTH BY THE SOMATROPIC AXIS: Growth Hormone and the Insulin-Like Growth Factors Have Related and Independent Roles, Andrew A. Butler, Annu. Rev. Physiol. 2001. 63:141–64

The following illustration demonstrates the current understanding and how it has eveolved away from circulating IGF-1 being important:

...

The Physiological Effects of Growth Hormone

GH is an anabolic hormone that induces positive nitrogen balance in intact animals and protein synthesis in muscle (45). At all ages, treatment of humans with human GH increases muscle size in GH-deficient individuals (45). Growth hormone enhances amino acid uptake into skeletal muscle, suggesting that this tissue is a primary target of the physiological effects of GH (45). However, other tissues may be important in the effect of GH on nitrogen balance. Furthermore, the effects of GH on nitrogen balance may or may not be mediated by IGF-I. GH therapy increases whole body protein synthesis (46) and enhances nitrogen retention, concomitant with the increase in lean body mass (47).

To determine whether the effects of GH on protein synthesis in muscle require IGF-I, the metabolic effects of GH, IGF-I and insulin were compared by infusing these factors into the forearms of human volunteers in whom systemic amino acid levels were held constant. All three factors enhanced phenylalanine balance. The uptake of phenylalanine was increased by GH and IGF-I, whereas phenylalanine release was inhibited by IGF-I and insulin, but not by GH (48). These studies strongly support the hypothesis that many of the anabolic effects of GH in muscle are dependent on IGF-I. On the other hand, IGF-I may have additional effects, such as inhibiting proteolysis. These and other studies imply that the effects of GH are mediated by local production of IGF-I, which acts in an autocrine/paracrine manner.

The long-term effects of GH include a decrease in deposition of fat and an increase in fat mobilization. Growth hormone exerts lipolytic effects on fat and muscle, and circulating free fatty acids and glycerol levels rise following acute administration of GH. This hormone also reduces fat mass, particularly in individuals who have accumulated excess fat during periods of GH deficiency (49). A similar effect occurs in adults treated with recombinant human GH (50), an effect that appears to be mediated by the inhibition of lipoprotein lipase (51, 52). GH administration also causes mild reductions in LDL cholesterol levels and small elevations in HDL cholesterol (53).

Acute administration in vitro of GH to fat and other tissue explants causes a temporary insulin-like effect on glucose uptake. In contrast, chronic GH treatment causes insulin resistance associated with hyperinsulinemia and a postreceptor defect in insulin signaling (54). The acute insulin-like effects of GH on carbohydrate metabolism are most likely independent of both IGF-I and insulin because these effects also occur in isolated tissue preparations and in cultured cells (55). The precise mechanism(s) by which GH regulates metabolism are not defined, but GH-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and/or IRS-2 may be involved (56). Ultimately, prolonged GH stimulation causes hyperglycemia associated with enhanced hepatic gluconeogenesis and glycogenolysis. These effects may be indirect results of GH-induced lipolysis and of elevated plasma free fatty acids that inhibit insulin activity at its target tissues. This type of lipotoxic effect was first noted by Randle and others and is known as the glucose/ fatty acid or Randle cycle (57).

Systemic administration of GH stimulates longitudinal bone growth and skeletal muscle growth, whereas IGF-I treatment preferentially increases the size of lymphoid tissues (spleen and thymus) and kidney (58). Growth hormone causes more robust longitudinal bone growth than IGF-I in animals, and the effects of these factors may be additive (59–61); furthermore, administration of recombinant human GH is more potent than that of recombinant IGF-I in humans (62). Systemic GH administration increases circulating levels of IGF-I, IGF-binding protein-3 (IGFBP-3), and the acid labile subunit (ALS). IGF-I administration, on the other hand, transiently increases circulating levels of IGF-I, inhibits GH secretion and may actually decrease levels of IGFBP-3 and ALS, thereby leading to faster clearance of IGF-I from the circulation. Indeed, this finding led to clinical trials using a complex of IGF-I/IGFBP-3 rather than IGF-I alone. Coadministration of IGFBP-3 with IGF-I to hypophysectomized rats markedly reduces the hypoglycemia associated with IGF-I treatment (63); however, the effects of co-administration of IGFBP-3 on the anabolic actions of IGF-I are variable and show [either] no change or an enhanced effect on growth (63).
...

length question

dat this is a great thread...so far i have read everything up until page 15...i just had a quick question for you?....how long would you say is the maximum length you can run the CJC/GHRP protocol for? i saw somewhere you recommended minimum of 6 weeks to a maximum of 12 weeks, but that was if the subject was on AAS...i wanted to know if that varied if the subject was not using AAS

liftbig18 said:

dat this is a great thread...so far i have read everything up until page 15...i just had a quick question for you?....how long would you say is the maximum length you can run the CJC/GHRP protocol for? i saw somewhere you recommended minimum of 6 weeks to a maximum of 12 weeks, but that was if the subject was on AAS...i wanted to know if that varied if the subject was not using AAS

Click to expand...

My only concern centered on CJC-1295 because it raises base GH levels on a chronic basis. The concern is mostly focused on the use of what I would deem large doses of CJC-1295. A large dose would be 3000mcg (3mg) to 4000mcg (4mg) per week. If you use such large doses I feel you need to take a break.

I really have no other concerns.

Using GHRP at 100mcg three times a day, even four or five does not specifically concern me.

Using modified GRF(1-29) (i.e. CJC-1295 w/o the DAC) at 100mcg three times a day, even four or five does not specifically concern me.

Using 2000mcg (2mg) per week of CJC-1295 does not (or at least no longer in my mind) raise a concern for pituitary hyperplasia leading to tumor formation. I am wary that the rise in base levels of GH is changing the pattern for males toward that of females... I am also wary of what chronically elevated base GH levels may mean in a very general way (ex. changing liver enzyme expression from male oriented to female)...

But I am not concerned about IGF-1 levels becoming extremely elevated.

In my opinion GHRPs can be used forever as well as modified GRF(1-29) at levels that restore GH to youthful levels.

For myself personally I have used GHRP-6 + either CJC-1295 or mod GRF(1-29) for nine months and counting...

...and I thank this character Datbtrue every damn day because no one that I meet believes I am almost 43 years old. Many even think I am in my late twenties. A youthful restoration for me means that starting a family at my age and being vital is now not only possible but also probable.

So when I read that someone is a naysayer and calls me an "armchair theorizer"... I try to work up some reaction (cus I kinda like to do that ) ...but really in truth...these days...I just smile and think "Man it would be really cool to flip a switch and go back in time ...erase all that I have ever conveyed ...and keep this stuff to myself."

appreciate the answer...so if someone was not to run the CJC and just run GHRP theoretically they could run it 3xed at 100mcgs each shot...for say six months take a few months off then start up again?....i am just starting to understand and research peptides now, thank you for the help

liftbig18 said:

appreciate the answer...so if someone was not to run the CJC and just run GHRP theoretically they could run it 3xed at 100mcgs each shot...for say six months take a few months off then start up again?....i am just starting to understand and research peptides now, thank you for the help

Click to expand...

You could run 100mcg of GHRP-6 3 times per day and do it forever.

You could also add any form of GHRH (except CJC) w/ it at 100mcg or more (no desensitization to GHRH) and do it forever.

Almost everything sold as CJC-1295 is really just modified GRF(1-29), so you could run it forever as described above.

If you do have CJC-1295 you can stop and think about how you want to run it.

Keep it rocking, loving this thread.

Will be starting my own GHRT this summer

What would be the dose of GHRP-6 for someone who wants to increase height at 165 pounds?

I was thinking about 150mcg at night, for 14 weeks.

Young One said:

What would be the dose of GHRP-6 for someone who wants to increase height at 165 pounds?

I was thinking about 150mcg at night, for 14 weeks.

Click to expand...

Your query is proceeded by a fundamental question.... "whether you can grow taller via increased supply of human growth hormone?"

The answer to that question is only relevant if your growth plates are still opened. If they are not no amount of human growth hormone or IGF-1 will increase the length of bones.

On the other hand if they are still open that means your puberty stage has not yet come to an end. In that case you are too young to be interacting with me. I have a rule (after having had to deal with at least a dozen communications from youngsters on this topic) that precludes me from interacting with teenagers on any level other then to warn them when they are endangering themselves.

Young One said:

What would be the dose of GHRP-6 for someone who wants to increase height at 165 pounds?

I was thinking about 150mcg at night, for 14 weeks.

Click to expand...

At 165 pounds you shouldn't take more than 75 mcg per injection.

DatBtrue said:

Systemic administration of GH stimulates longitudinal bone growth and skeletal muscle growth, whereas IGF-I treatment preferentially increases the size of lymphoid tissues (spleen and thymus) and kidney (58).

Click to expand...

Dat,

Given the IGF-like actions of PEG-MGF that we have already discussed, do you think it is possible to grow your organs with PEG-MGF?

Moose069 said:

Dat,

Given the IGF-like actions of PEG-MGF that we have already discussed, do you think it is possible to grow your organs with PEG-MGF?

Click to expand...

Yes. But in the way a hobbiest bodybuilder would use it I don't think it is likely to create a sustained increase in size. Increased proliferation and decreased apoptosis are the mechanisms of IGF-1. Remove IGF-1 and the rate of apoptosis will resume so the organ should decrease in size.

Places like the intestinal mucosal lining are likely to be effected. There are a lot of receptors there. However the the small intestinal epithelial lining is
normally replaced every 3–6 days in humans. So when IGF-1 acts it is likely to reduce hypoplasia (or loss of cells) and in some situations this wouldn't be bad.

For me it served as tissue regeneration and when several courses of IGF-1 LR3 were removed that lining returned to the same turnover rate. But for some reason I restrengthened that lining permanently. I didn't have any perceivable "gut growth" so IGF-1's effect on that organ was positive tissue regeneration.

Now if we chronically administer IGF-1 or chronically elevate it we can induce straight-up organ growth and this would not be positive.

I know you think IGF-1 is ineffective by itself, what if you combined it with IGF-2? and the ghrs a couple times a week?

WC114 said:

I know you think IGF-1 is ineffective by itself, what if you combined it with IGF-2? and the ghrs a couple times a week?

Click to expand...

You don't want to mess with IGF-2 (IGF-II). Besides IGF-2 is NOT the missing ingredient to make IGF1 effective.

The missing ingredient is Growth Hormone. You want to grow more muscle use more Growth Hormone.

Why? Growth Hormone is a vehicle which creates IGF-1 in ways you can never duplicate by injecting IGF-1. Systemically it increases liver derived (endocrine) IGF-1 and both the binding protein that protects IGF-1, shepherds it and controls its use as well as Acid Labile Subunit which binds to both IGF-1 & the binding protein to form a complex.

But even this is NOT extremely important as it pertains to muscle growth.

What is important is that Growth Hormone causes IGF-1 to be synthesized within a muscle cell. IGF-1 pools in the cytoplasm and either prebinds to a receptor before rising to the surface or makes its way to the surface and binds to an open receptor on the same or neighboring cell.

What is important is that Growth Hormone causes MGF (a derivative of IGF-1) to be synthesized within a muscle cell. But unlike IGF-1, MGF moves to the nucleus of the cell to mediate its events (i.e. activate proliferation).

All of this activity is called autocrine/paracrine and means basically locally made locally used. As you can see a huge part of the "local" is within the cell giving birth. Some of the "local" is in neighboring cells.

Injecting IGF-1 (even if it stays within muscle for a while ...and that means outside muscle cells NOT within them) is NOT the same thing. That is why experiments that cause IGF-1 and/or MGF to be created and expressed within a muscle cell result in huge muscle growth, while injected IGF-1 does not.

Wounds are different. Circulating platelets which contain several healing growth factors & checks, including IGF-1 are drawn to wounded tissue and "sticky there" (I apologize for not having the name of the substance that brings about the "stickiness" in my mind at the moment).

This is not the same thing as injecting IGF-1 locally. There remains the possibility that injecting IGF-1 near wounds results in more IGF-1 being "stuck" .

So how can you increase muscle growth?

First by not wasting money on IGF-1.

Second by dramatically increasing Growth Hormone during periods when you are in an anabolic state (i.e. on cycle). By dramatically I mean you need to approach 15iu a day.

Will a few iu or even 5iu make a difference in IGF-1 expression? Sure it will. Over time you will notice a difference, with the effect being more dramtic in older guys.

But if you want to grow like the big boys there are certain things you must do. They are steroids/insulin/GH (high levels).

Now there are things that can be done to:

- make your androgen receptors transcribe more (i.e. be more active per receptor) in which case you need less steroids for a given effect.

- there are more optimal ways to use GH which will allow you to get more our of it (think 100mcg GHRP-6 + small amount of 1.5iu (maybe 2iu) of GH every three hours 8 times a day).

- make your body more anabolic by "priming" before a cycle ...meaning diet into single digit body fat levels (which reduces the amount of aromatizing "events" which will occur on cycle due to a larger fat pad & being lean skews nutrient partioning toward muscle)

- properly use exogenous insulin or find an alternative (ex. Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose, Dionysia Kalogeropouloua, Metabolism Clinical and Experimental 57 (2008) 1747–1752)

- Etc.

But simply injecting IGF-1 and IGF-2 will do very little for you other then increase your cancer risk. Sure you will be experiencing decent glucose disposal ...but why use these things for that?

Enough on this topic....

...but let me add when people go and read Grunt's advise on IGF-1 LR3 where he refers to the term autocrine/paracrine, that terminology is misapplied.

IGF-1 administration negates GHRPs & hinders GHRH's GH release

Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Growth Hormone (GH) Secretion, Both Spontaneous and Stimulated by GH Releasing Hormone or Hexarelin, a Peptidyl GH Secretagogue, in Humans, E. Ghigo, J Clin Endocrinol Metab 84: 285–290, 1999

ABSTRACT

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS (Somatostatin) and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin.

We studied the effects of rhIGF-I administration (20 mg/kg sc at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 mg/kg iv at + 180 min) or Hexarelin (HEX, 2.0 mg/kg iv at + 180 min), a GHS, in eight normal young women (age, mean 6 SEM, 28.3 +- 1.2 yr; body mass index, 20.1 +- 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 +- 30.5 vs. 274.4 +- 25.3 mg/L, P , 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)0–300 min 140.6 +- 66.3 vs. 114.6 +- 32.1 mg/L.h], whereas it inhibited the GH response to both GHRH (AUC180–300 min 447.7 +- 159.4 vs. 715.9 +- 104.3 mg/L.h, P , 0.05) and HEX (620.3 +- 110.4 vs. 1705.9 +- 328.9 mg/L.h, P , 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 +- 12.8%) was lower than that on the response to HEX (57.7 +- 11.0%). In fact, the GHresponse toGHRHalone was clearly lower than that to HEX alone (P,0.05), whereas the GH responses to GHRH and HEX were similar after rhIGF-I.

Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.

DatBtrue said:

- make your androgen receptors transcribe more (i.e. be more active per receptor) in which case you need less steroids for a given effect.

Click to expand...

Care to expand on that?

Damn 15iu's per day. I thought I was going big with 15iu's 3x per week.

fourthgen said:

Damn 15iu's per day. I thought I was going big with 15iu's 3x per week.

Click to expand...

Injections seperated to 8 times per day though. Not 3 times per week.

likkayouth said:

Care to expand on that?

Click to expand...

i've tried to get that out of him too...maybe you'll have better luck!