What should I use? ...and why?
GH Releasing System Simplified
datbtrue

Three Basic Hormones

Form a V w/ your fingers you have the basics for the GH releasing system modeled before you. One finger is a hormone called Growth Hormone Releasing Hormone (GHRH) and the other is the hormone Somatostatin.

The bottom of the V is where both of those hormones converge. At that bottom we have somatotrophs (or somatotropes or Growth Hormone Releasing cells). These are cells that spend most of their time assembling Growth Hormone (GH) from pieces and storing it.

So in this simple system we have three hormones. We have Growth Hormone Releasing Hormone (GHRH) which comes from the brain and contacts Growth Hormone Releasing Cells (Somatotrophs or somatotropes) and causes the cell to release some of the Growth Hormone (GH) it has made and stored. If we ask the cell to release GH all the time we end up with no storage of GH. As soon as some is made it is released. This is what I call GH bleed because you get a constant low flow or dribble of GH but no big pulse, or mass of GH.

What causes GH release? The brain-derived hormone Growth Hormone Releasing Hormone (GHRH). So if GHRH is always free to act we end up with GH bleed.

However the other brain-derived hormone Somatostatin functions as the "off switch". It also contacts the Growth Hormone Releasing Cell (Somatotroph) and instructs it not to release Growth Hormone (GH). If Somatostatin is present and GHRH is not then we will never have GH release. What we will have is plenty of time for the cells to make and store GH. If we could ever get Somatoststin to go away and GHRH to show up we'd have a big release or pulse of GH.

As you can see both the "on switch" hormone Growth Hormone Releasing Hormone (GHRH) and the "off switch" hormone Somatostatin are necessary or we end up with a malfunctioning human being.

You may wonder if we can limp by w/ just GH bleed. We can up until puberty when it is time to grow, develop and mature. Growth, development and maturity requires pulsatile GH (in conjunction with timed release of sex hormones).


You may also wonder what happens if GHRH and Somatostatin are together at the bottom of the V at the same time. What does the cell do? The answer is that for the most part Somatostatin is stronger and GH will not be released.

From this it is easy to see that a well-functioning GH releasing system depends on both GHRH & Somatostatin. Somatostatin to hold back release so enough GH can be made and then GHRH to cause a pulse of GH. Not only must these two brain-derived hormones which oppose each be active, they also must alternate with one another...GHRH release and a while later somatostatin and then a while later somatostatin retreats and GHRH is released again... this brings release of some of the GH mass that has been built up over the course of 3 hours in what looks like a pulse if graphed.

Ghrelin (GHRPs) the 4th hormone in the GH Releasing System

To be complete we need to add a fourth hormone to this system. One hormone Growth Hormone (GH) is the end-product hormone. It results from all of this activity. That leaves the other 3 hormones as hormones that determine how, when and how much GH will be released.

If you replace the V you formed with your fingers with a Y, by using the same two fingers to form a V and now adding your long forearm, you have a very good model of the GH releasing system.

The forearm extends to the stomach and that is where the hormone Ghrelin is made. Ghrelin is a hunger derived gut-hormone. It is capable of making its way to the pituitary where the GH releasing cells (somatotrophs) reside. Just like GHRH & Somatostatin it also can contact the cell. When it does it reduces Somatostatins effect. Ghrelin increases GH release. It does this in several ways -by encouraging the brain to release more GHRH, amplifying the effect of GHRH when it gets to the somatotroph, benefiting from GHRH being at the cell to amplify Ghrelin's own effect which is in part an increase in GH release and countering Somatostatin's stoppage effect at the cell.

In fact Ghrelin can cause GH release all by itself even if Somatostatin is around. But Ghrelin makes the environment safe for GHRH to act and if GHRH acts when Ghrelin is there the result is what is called a synergistic GH release. Synergy means the amount is larger then each could have produced on its own. If Ghrelin would cause 5 units to be released and GHRH 2 units when you put them together synergy means the result is more then additive (5 + 2). The synergistic result may be 15 units. Why does synergy happen? GHRH and GHRP help each other... they make each other stronger. More complete fuller treatment of the topic available on the forum.

Ghrelin is a natural hormone with effects besides GH release. Now a synthetic form of Ghrelin which primarily just effects GH release is what is known as Growth Hormone Releasing Peptides (GHRPs). These are man made and are capable of contacting the somatotrophs and causing GH release the same as Ghrelin.

Originally they were called Secretagogues to include a few non-peptide structures as well. So Growth Hormone Releasing Peptides may be thought of in our Y model as replacing Ghrelin. They differ from GHRH primarily in the color I chose. Consistently through most of my posts over the years I label them purple and GHRH I label green. Wake up! GHRPs are the 3rd hormone/peptide that effects GH release. Its presence at the somatotroph causes GH release on its own and with the naturally occurring "on switch" it amplifies GH release. By stopping somatostatin GH is released. Now GHRPs never result in GH bleed. The release they trigger is always a pulse that is over with within 3 hours.

Will IGF-1 interfere with all of this?

Not really IF you are supplying external GHRH and external GHRPs. IGF-1 primarily exerts negative feedback by increasing somatostatin release. Somatostatin is stopped by GHRPs. IGF-1 can also reduce release of natural GHRH from the brain. This is overcome by supplying external GHRH.

What is CJC-1295, CJC-1293, GRF(1-29), Sermorelin and modified GRF(1-29)?

In short they are all forms of GHRH (Growth Hormone Releasing Hormone).


What are GHRP-6, GHRP-2, Ipamorelin, Hexarelin?

In short they are all forms of GHRPs (Growth Hormone Releasing Peptides, Ghrelin-mimetics)

How do I chose? What do I do?
Step one] Again since you don't know if somatostatin is around you are rolling the dice by injecting GHRH. There will be zero GH release if somatostatin is around and only some if somatostatin is just starting up or just diminishing. Only if you are lucky to inject when somatostatin is gone will there be decent GH release. To overcome this, very large amounts say 2mg (2000mcg) are sometimes used. Injecting GHRH alone is not very effective.

Step two]
Step three]
Step four]How many times can I dose before I lose pulsation? Six (6) a day every 3 hours

How few times can I do it for some better sleep, small anti-aging effect? Just pre-bed.

Step five]
Step six]
What are all these peptides and what should I choose?

First notice that I referred to GHRH, GH and Ghrelin as hormones. They are naturally occurring hormones whose structure is just one amino acid such Arginine bonded to another amino acid such as Lysine. They are both hormones and peptides. Sex hormones are examples of hormones that are not built in the body with amino acids.

Now GHRPs do not naturally occur in the body but since they are mimickers of a hormone Ghrelin we can fudge and use the term hormone if we want. Growth Hormone Releasing Petites (GHRPs) as the name implies are built with attachments of amino acids.

Which GHRH?

The body makes GHRH which 44 aminos long. 15 amino acids are useless so the first 29 amino acids is what is known as GRF(1-29). Yes GHRH(1-29) makes more sense but someone chose G for "growth hormone", R for "releasing" and F for "factor". The numbers just tell you which amino acids from GHRH are kept.

GRF(1-29) acts just like GHRH so I'll color it green. GRF(1-29) is an FDA-approved pharmaceutical drug named Sermorelin.

So GHRH, GRF(1-29) and Sermorelin are basically the same. The problem though is they are easily eaten up by blood enzymes within minutes. If you could inject directly into the pituitary at the base of the brain then they will be effective, after-all that is what the brain drops into the pituitary. But circulating in the blood means they are rendered ineffective within minutes.

That leaves us with analogs. An analog is a modification(s) to the peptide such that a property(ies) is(are) changed such as longer half-life, receptor binding affinity or receptor binding strength w/o losing the action. Many analogs can and have been made. However all you need is an analog that survives early blood plasma enzyme death and lasts say 30 minutes. Note a receptor is how some hormones/peptides interact with a cell. The hormone/peptide binds to a receptor on the outside of the cell and the message carried in. I purposely avoided receptor talk so as to avoid confusion and substituted the term "contact" and "contact with the cell".

IGF-1 LR3 is an analog of IGF-1. It survives longer in plasma w/o binding to a binding protein but also has a lower binding affinity for its contact with the cell or better yet IGF-receptor.

CJC is a term coined & used in a study that tested a newly created velcro type drug complex to attach to GRF(1-29) to allow it to cling to albumin in blood and give it protection and a long life (albumin has a very long plasma life).

They tested three peptides/drug compounds. The first was simply GRF(1-29) with the drug affinity complex (DAC) attached. Think of that DAC as simply the velcro drug component. As you can see the CJCs are not pure peptides. They called this CJC-1288. It lasted about the same as plain old GRF(1-29). Blood plasma enzymes killed it in minutes.

Then they took GRF(1-29) and made one amino acid swap plus the DAC (velcro drug) That means they took Arginine in the 2nd position of the peptide and replaced it with its mirror image form known as the D form. This makes the analog peptide stronger but not by enough. The half-life is maybe double GRF(1-29) in humans. So 5 minutes of half-life. This they called CJC-1293.

Then they made 4 amino acid changes in GRF(1-29) to really strengthen it so it would last more then 30 minutes and added the drug affinity complex. This worked well for them because the peptide/drug hybrid lasted long enough to find the plasma albumin for the DAC part to velcro itself to for a long life of several days. This they called CJC-1295

You want none of the CJC's. The first two because they do not survive long enough and the last one because it is always around. True somatostatin does pop up and stop GH release, but as soon as it can CJC-1295 is inducing GH release. The study itself found it increased base levels but did not increase pulses. That means there is less GH mass synthesized and stored in the somatotrophs. What are somatotrophs? Remember they are growth hormone releasing cells.

Somatotrophs are not cells that release prolactin. Prolactin is released by Lactotrophs. Somatotrophs self organize into networks that coordinate GH release into a pulse. A fuller treatment is available on this forum.

What do you want?

You want the pure peptide part that was used in the third analog. You want those 4 modifications because they make what is essentially GHRH last for 30 minutes or more. This is a fine peptide to contribute to a GH pulse. This I call modified GRF(1-29). Since it is basically a 30 minute plus lasting GHRH I color it green.

Which GHRP?

GHRP-6 is sloppier in that it activates a wider array of effects beyond GH release. It causes intense hunger and gastic motility. It can have a mild effect on cortisol and prolactin. It is a first generation GHRP.

GHRP-2 is less sloppy with a more intense GH release, no gastric motility and less hunger effect. It can have an effect within the normal range on prolcatin and cortisol. It is a second generation peptide.

Ipamorelin is not sloppy at all. It does not release as much GH as GHRP-2 but it causes virtually no hunger or gastric motility and for the most part does not effect cortisol or prolactin. It is a third generation peptide

You would choose GHRP-2 unless you wanted GHRP-6 for the hunger effect or for the lower release profiles. You would choose GHRP-2 normally as the most bang for the buck.

If you are very sensitive to perturbations in cortisol or prolactin you would choose the more expensive Ipamorelin.

I use either GHRP-2 or Ipamorelin with modified GRF(1-29) I usually rotate around.