h2s
11-15-2012, 08:40 AM
UNDERSTANDING GHRP + GHRH PEPTIDES
An Introduction By: h2s
This will be a guide for those looking to do research on GHRP/GHRH. It is not to be considered a complete source, and I highly recommend advanced research beyond the context of this article previous to using these peptides. With the wealth of knowledge available across the internet, there is no reason not have a solid understanding of the mechanisms behind these peptides before using them. This guide will be pretty lengthy, so it won’t replace the spoon-fed info type guides. It is meant for those who want to understand a bit of what is going on.
A short disclaimer:
This guide is purely hypothetical, and I do not encourage the use of any PED without the close guidance of a physician. This guide takes no consideration to the laws of your country. I do not condone any illegal activity. It is merely designed to be an educational resource. This guide also does not condone the usage of Research Chemical company's products. These products are strictly for research use only, and human usage is in violation of their terms of service. I also in no way am portraying myself as an expert on peptides. This guide is the result of my own personal investigating and research for my own experimentation, which I compiled to be able to share with others.
I also would like the time to thank Dat, and his wonderful board. Dat's writing has been the foundation of most of my research and certainly the fuel for my curiosity. I would also like to thank the 3 guys I had look it over. You know how much I appreciate all your assistance with my personal research.
As we begin, let’s cover some of the basics:
What is a peptide?
Peptides, to be brief, are molecules formed by linking two or more amino acids via peptide bonds. These can vary greatly in size, from a peptide consisting of two amino acids, referred to as dipeptides, to much more complex, such as Human Growth Hormone (HGH) which is a larger peptide which consists of 191 amino acids.
What is Human Growth Hormone?
This, as you can probably assume, could fill another 100 guides with info, so I will stay with a stricter definition. Human Growth Hormone is a large peptide, consisting of 191 amino acids, released from the pituitary gland found in the brain (see image).
http://i.imgur.com/HzjtJ.jpg
It is released from the pituitary gland in “pulses” as a response to stimulation from Growth Hormone Releasing Hormone, or GHRH. In the body, HGH has many effects such as cell reproduction, increased muscle mass, lipolysis, protein synthesis, and many other functions. I highly recommend that someone who is interested in learning more about Human Growth Hormone, or considering supplementing with it and/or its Secretagogues, do more research into its role in the body.
What is GHRH?
http://i.imgur.com/I97e6.png?1
CJC-1295
GHRH, or growth hormone releasing hormone, is a naturally occurring 44 amino acid peptide, which binds to the GHRHR, or growth hormone releasing hormone receptor, found on cells in the pituitary gland. Binding to the GHRHR signals the pituitary gland to secrete stored growth hormone.
What is GHRP?
http://i.imgur.com/prxMb.gif?1
Ipamorelin
GHRP, or growth hormone releasing peptide, refer to a group of synthetic peptides that act as Ghrelin mimetics. These peptides bind to GHS-R, which will have a positive effect on growth hormone release. Growth Hormone Releasing Peptides, along with the natural Ghrelin, are commonly termed Growth Hormone Secretagogues.
What is Somatostatin?
http://i.imgur.com/OjE5f.png
Somatostatin
Somatostatin, which can also be referred to as GHIH or Growth Hormone Inhibiting Hormone, is an inhibitory peptide of Growth Hormone, and directly opposed the actions of GHRH. The relationship between GHRH and Somatostatin in the brain works in balance. GHRH, as explained earlier, causes the pituitary to release GH. If GHRH were to continually act upon GHRHR, one would experience GH Bleed, a topic that will be touched upon shortly. To counter this, Somatostatin also acts on Somatotropic cells (Growth Hormone releasing cells) and causes an inhibition to release of GH. If only Somatostatin was present, the pituitary would not release any GH. As you can see, both of these peptides are important in the regulation of growth hormone release in the body.
What is Ghrelin?
Ghrelin is a 28 amino acid peptide, originating from the stomach and pancreas. Ghrelin plays a role in stimulating hunger. It also increases fat mass. The Ghrelin mimetics, fortunately, do not share this trait. More importantly for our understanding, Ghrelin plays a vital role in the balance between the growth hormone release and Somatostatin.
Moving Forward...
If you have a basic understanding of the different characters at play above, then we can move on and talk about what role these peptides are taking on when administered. In order to understand HGH's release in the body, it is vital to understand the concept of pulsing.
What is a pulse? Why should I care?
In the natural process...
The pituitary gland synthesizes HGH and stores it until instructed to release. When instructed to release, through GHRH binding to the GHRHR, a "pulse" or release of HGH stored in the pituitary, will occur. Note that a pulse does not empty the pituitary of all of its stored HGH. Now, in the presence of just GHRH, Growth hormone would continually be released from the pituitary, and we would not have a "pulse." This is where Somatostatin comes into play, to inhibit further release of HGH. The process simplified looks like:
GHRH ----> HGH release from pituitary -----> Somatostatin -----> HGH release discontinued
|----------Release Stored HGH--------------|-----------------Store HGH----------------|
It is important to understand that you are NOT supplying exogenous HGH when utilizing peptides. Instead, you are causing your body to create pulses (large magnitude) from its own HGH. For this reason you want to mimic the patterns of the body's natural pulse rhythm. Use this way will prevent desensitation and will allow your body to maintain its natural balance (as opposed to overworking it). This is believed to also be quite a bit more effective in terms of your body's response and will be better at supporting weight increase (Ref (http://www.ncbi.nlm.nih.gov/pubmed/3968505)), a good sign of desensitation from continuous usage.
For this reason, you want to avoid two things:
Dosing more frequently than every 3 hours (approximate natural time in between pulses)
GH Bleed
What is "GH Bleed"?
The term "GH Bleed" refers to a state in which HGH is continuously released from Somatotrophs (Growth Hormone releasing cells). GH Bleed can occur from constant stimulation of GHRH (Primarily caused from the utilization of CJC-1295 (will be further discussed later in this article)). This is to be avoided for two significant reasons. The first, is that the Somatotrophs will be constantly labored to produce the excess HGH and will no longer be able to communicate as "network" as is natural for these cells through the pituitary. This will lower their responsiveness and the effectiveness of pulses. The second is that it is believed the body should respond much more effectively to a pulsatile distribution of HGH as opposed to a low constant supply.
What actually happens when I administer GHRP and GHRH?
*In the interest of keeping this a "simple" guide, I will not go into the pathways of the receptor activation and the effects exerted. If interested, there is a lot of information on the subject available throughout the web.
At this time you should be able to see where this is going, and why administration of these peptides can be beneficial in terms of growth hormone release. But how does it actually happen?
*Quick note, at this point we will discuss GHRP and GHRH in the general sense. Later we will discuss which individual peptides to consider for you
Upon administration of GHRH, it will travel to the anterior pituitary gland and stimulate GHRHR, which, assuming the absence of Somatostatin, will stimulate the release of growth hormone.
Upon administration of GHRP, it will have two effects relevant to our cause. The first, is it will promote the release of GHRH, which will in turn cause the release of growth hormone. GHRP will also directly interact with the GHS-R (or Growth Hormone Secretagogue Receptor), which will also positively affect the release of HGH. GHRP also has the benefit of directly opposing (and, thus, inhibiting) Somatostatin.
In terms of effects on release, it is believed that GHRP increases the number of cells releasing HGH, but not the amount those cells release. GHRH, on the other hand, is believed to increase both the number of cells that are releasing HGH, as well as the amount they are releasing.
To summarize this process in a simplistic manner:
GHRP -----> Release GHRH, Increase number of somatotropes releasing HGH, inhibit Somatostatin
GHRH -----> Increase numer of somatotropes releasing HGH, Increase amount of HGH release per Somatotropes
So, should I run just one of these peptides?
No. There is a synergy between coadministration of GHRP and GHRH that is not advisable to forego. The cumulative effect between these two becomes not the total of the individual parts, but a greater response caused by the synergy of their independent actions. GHRH can cause a pulse of HGH, but will not be effective if Somatostatin is present at the time of administration. The addition of the GHRP will inhibit the effects of the present Somatostatin allowing for the pulse to be successful. The single administration of GHRP can create a pulse on its own (greater than that of GHRH alone), but will not reach its potential had GHRH been administered at the same time.
If for whatever reason you can only run one peptide, it is advisable to use a GHRP, since a GHRP will always illicit some action, whereas a GHRH can cause no effect in the presence of Somatostatin.
Which GHRH should I choose?
The choice in GHRH is quite simple: tetrasubstituted GRF (1-29). This GHRH is also commonly sold as mod grf(1-29), CJC-1295 without DAC, or CJC-1293. Mod grf(1-29) is ideal in that it has an appropriate half-life to support a healthy pulse, and will not cause HGH Bleed.
What about CJC-1295, also known as CJC-1295 with DAC?
This GHRH is to be avoided. To understand the difference, understand that CJC-1295 w/ DAC is similar to mod grf(1-29) with the exception of the addition of the DAC, or Drug Affinity Complex. This addition was designed to increase the half-life of GHRH significantly. The issue with using a GHRH that has such a long half-life is that its constant presence will lead to GH Bleed. As mentioned previously, GH Bleed is undesirable as it leads to reduction in pulse strength of HGH release, a constant release of HGH, and overworks the cells impeding on their ability to communicate as a network.
Which GHRP should I use?
This is where the choice becomes a bit more personal. There are three peptides that are readily available GHRPs to choose from: GHRP-6, GHRP-2, and Ipamorelin.
GHRP-6 has an effect on GH release, increases hunger, causes gastric emptying, and increases cortisol and prolactin.
GHRP-2 has a stronger effect on GH release, does not increase hunger or cause gastric emptying as much as GHRP-6, and increases cortisol and prolactin.
Ipamorelin has a lessened effect on GH release, but in turn has no substantial effect on hunger, gastric emptying, cortisol, or prolactin.
If you are sensitive to, or would like to avoid the increase of either cortisol or prolactin, it would be advisable to choose the more expensive Ipamorelin.
If not, the stronger effect of the GHRP-2/6 would probably be a better choice. GHRP-6 should be chosen if the benefit of increased hunger would correlate with your goals. Elsewise, the increased effect of the GHRP-2 would probably suit you best.
How do I reconstitute the Peptides?
I personally recommend reconstitution with Bacteriostatic water. For instruction on how to reconstitute peptides, please see my other guide: Understanding Reconstitution: A Simple Guide (http://www.swolesource.com/forum/human-growth-hormone-peptides/202-understanding-reconstitution-simple-guide.html)
How are these peptides administered?
Peptides are administered through a subcutaneous injection with an insulin syringe (29g-31g). Subcutaneous (under the skin) injections are performed, most commonly on the abdomen, by pinching an area of fat and inserting the needle at a 45 degree angle (may be done at other angles depending on body fat). Once inserted, it is advisable to aspirate (pull back slightly on the plunger to make sure no blood is present, a sign that you are in a vein). Assuming no blood is present, the peptides can be injected.
More information on injection technique can be found here: (Warning: PDF) (http://www.cc.nih.gov/ccc/patient_education/pepubs/subq.pdf)
How often should I administer the peptides?
This is an entirely personal question, and will vary depending on goals and injection frequency tolerance of a user.
The standard protocol has been (on average) dosing 3 times a day (AM, post-workout (or pre-cardio), and pre-bed).
For those that choose to only administer once a day, pre-bed administration is most advisable.
Once daily dosing is typically utilized for the benefits in rest, rejuvenation and anti-aging.
More frequent dosing is considered much more ideal in terms of fat loss and muscle gain.
The general rule of thumb with frequent administration is to not dose more frequently than every 3 hours, as presented earlier.
Anything to consider when dosing?
You will want to dose on an empty stomach, or at least in the absence of fats and carbohydrates, both of which can blunt the body's release of HGH. You also want to avoid eating for approximately a half hour post administration in order to allow the pulse to reach its peak.
Final Note
Experimentation is key to finding a protocol that works for you. Peptides can be a great addition to any hormonal cycle (where, imo, they really shine) or even run as solo products.
Good luck with your research.
-h2s
An Introduction By: h2s
This will be a guide for those looking to do research on GHRP/GHRH. It is not to be considered a complete source, and I highly recommend advanced research beyond the context of this article previous to using these peptides. With the wealth of knowledge available across the internet, there is no reason not have a solid understanding of the mechanisms behind these peptides before using them. This guide will be pretty lengthy, so it won’t replace the spoon-fed info type guides. It is meant for those who want to understand a bit of what is going on.
A short disclaimer:
This guide is purely hypothetical, and I do not encourage the use of any PED without the close guidance of a physician. This guide takes no consideration to the laws of your country. I do not condone any illegal activity. It is merely designed to be an educational resource. This guide also does not condone the usage of Research Chemical company's products. These products are strictly for research use only, and human usage is in violation of their terms of service. I also in no way am portraying myself as an expert on peptides. This guide is the result of my own personal investigating and research for my own experimentation, which I compiled to be able to share with others.
I also would like the time to thank Dat, and his wonderful board. Dat's writing has been the foundation of most of my research and certainly the fuel for my curiosity. I would also like to thank the 3 guys I had look it over. You know how much I appreciate all your assistance with my personal research.
As we begin, let’s cover some of the basics:
What is a peptide?
Peptides, to be brief, are molecules formed by linking two or more amino acids via peptide bonds. These can vary greatly in size, from a peptide consisting of two amino acids, referred to as dipeptides, to much more complex, such as Human Growth Hormone (HGH) which is a larger peptide which consists of 191 amino acids.
What is Human Growth Hormone?
This, as you can probably assume, could fill another 100 guides with info, so I will stay with a stricter definition. Human Growth Hormone is a large peptide, consisting of 191 amino acids, released from the pituitary gland found in the brain (see image).
http://i.imgur.com/HzjtJ.jpg
It is released from the pituitary gland in “pulses” as a response to stimulation from Growth Hormone Releasing Hormone, or GHRH. In the body, HGH has many effects such as cell reproduction, increased muscle mass, lipolysis, protein synthesis, and many other functions. I highly recommend that someone who is interested in learning more about Human Growth Hormone, or considering supplementing with it and/or its Secretagogues, do more research into its role in the body.
What is GHRH?
http://i.imgur.com/I97e6.png?1
CJC-1295
GHRH, or growth hormone releasing hormone, is a naturally occurring 44 amino acid peptide, which binds to the GHRHR, or growth hormone releasing hormone receptor, found on cells in the pituitary gland. Binding to the GHRHR signals the pituitary gland to secrete stored growth hormone.
What is GHRP?
http://i.imgur.com/prxMb.gif?1
Ipamorelin
GHRP, or growth hormone releasing peptide, refer to a group of synthetic peptides that act as Ghrelin mimetics. These peptides bind to GHS-R, which will have a positive effect on growth hormone release. Growth Hormone Releasing Peptides, along with the natural Ghrelin, are commonly termed Growth Hormone Secretagogues.
What is Somatostatin?
http://i.imgur.com/OjE5f.png
Somatostatin
Somatostatin, which can also be referred to as GHIH or Growth Hormone Inhibiting Hormone, is an inhibitory peptide of Growth Hormone, and directly opposed the actions of GHRH. The relationship between GHRH and Somatostatin in the brain works in balance. GHRH, as explained earlier, causes the pituitary to release GH. If GHRH were to continually act upon GHRHR, one would experience GH Bleed, a topic that will be touched upon shortly. To counter this, Somatostatin also acts on Somatotropic cells (Growth Hormone releasing cells) and causes an inhibition to release of GH. If only Somatostatin was present, the pituitary would not release any GH. As you can see, both of these peptides are important in the regulation of growth hormone release in the body.
What is Ghrelin?
Ghrelin is a 28 amino acid peptide, originating from the stomach and pancreas. Ghrelin plays a role in stimulating hunger. It also increases fat mass. The Ghrelin mimetics, fortunately, do not share this trait. More importantly for our understanding, Ghrelin plays a vital role in the balance between the growth hormone release and Somatostatin.
Moving Forward...
If you have a basic understanding of the different characters at play above, then we can move on and talk about what role these peptides are taking on when administered. In order to understand HGH's release in the body, it is vital to understand the concept of pulsing.
What is a pulse? Why should I care?
In the natural process...
The pituitary gland synthesizes HGH and stores it until instructed to release. When instructed to release, through GHRH binding to the GHRHR, a "pulse" or release of HGH stored in the pituitary, will occur. Note that a pulse does not empty the pituitary of all of its stored HGH. Now, in the presence of just GHRH, Growth hormone would continually be released from the pituitary, and we would not have a "pulse." This is where Somatostatin comes into play, to inhibit further release of HGH. The process simplified looks like:
GHRH ----> HGH release from pituitary -----> Somatostatin -----> HGH release discontinued
|----------Release Stored HGH--------------|-----------------Store HGH----------------|
It is important to understand that you are NOT supplying exogenous HGH when utilizing peptides. Instead, you are causing your body to create pulses (large magnitude) from its own HGH. For this reason you want to mimic the patterns of the body's natural pulse rhythm. Use this way will prevent desensitation and will allow your body to maintain its natural balance (as opposed to overworking it). This is believed to also be quite a bit more effective in terms of your body's response and will be better at supporting weight increase (Ref (http://www.ncbi.nlm.nih.gov/pubmed/3968505)), a good sign of desensitation from continuous usage.
For this reason, you want to avoid two things:
Dosing more frequently than every 3 hours (approximate natural time in between pulses)
GH Bleed
What is "GH Bleed"?
The term "GH Bleed" refers to a state in which HGH is continuously released from Somatotrophs (Growth Hormone releasing cells). GH Bleed can occur from constant stimulation of GHRH (Primarily caused from the utilization of CJC-1295 (will be further discussed later in this article)). This is to be avoided for two significant reasons. The first, is that the Somatotrophs will be constantly labored to produce the excess HGH and will no longer be able to communicate as "network" as is natural for these cells through the pituitary. This will lower their responsiveness and the effectiveness of pulses. The second is that it is believed the body should respond much more effectively to a pulsatile distribution of HGH as opposed to a low constant supply.
What actually happens when I administer GHRP and GHRH?
*In the interest of keeping this a "simple" guide, I will not go into the pathways of the receptor activation and the effects exerted. If interested, there is a lot of information on the subject available throughout the web.
At this time you should be able to see where this is going, and why administration of these peptides can be beneficial in terms of growth hormone release. But how does it actually happen?
*Quick note, at this point we will discuss GHRP and GHRH in the general sense. Later we will discuss which individual peptides to consider for you
Upon administration of GHRH, it will travel to the anterior pituitary gland and stimulate GHRHR, which, assuming the absence of Somatostatin, will stimulate the release of growth hormone.
Upon administration of GHRP, it will have two effects relevant to our cause. The first, is it will promote the release of GHRH, which will in turn cause the release of growth hormone. GHRP will also directly interact with the GHS-R (or Growth Hormone Secretagogue Receptor), which will also positively affect the release of HGH. GHRP also has the benefit of directly opposing (and, thus, inhibiting) Somatostatin.
In terms of effects on release, it is believed that GHRP increases the number of cells releasing HGH, but not the amount those cells release. GHRH, on the other hand, is believed to increase both the number of cells that are releasing HGH, as well as the amount they are releasing.
To summarize this process in a simplistic manner:
GHRP -----> Release GHRH, Increase number of somatotropes releasing HGH, inhibit Somatostatin
GHRH -----> Increase numer of somatotropes releasing HGH, Increase amount of HGH release per Somatotropes
So, should I run just one of these peptides?
No. There is a synergy between coadministration of GHRP and GHRH that is not advisable to forego. The cumulative effect between these two becomes not the total of the individual parts, but a greater response caused by the synergy of their independent actions. GHRH can cause a pulse of HGH, but will not be effective if Somatostatin is present at the time of administration. The addition of the GHRP will inhibit the effects of the present Somatostatin allowing for the pulse to be successful. The single administration of GHRP can create a pulse on its own (greater than that of GHRH alone), but will not reach its potential had GHRH been administered at the same time.
If for whatever reason you can only run one peptide, it is advisable to use a GHRP, since a GHRP will always illicit some action, whereas a GHRH can cause no effect in the presence of Somatostatin.
Which GHRH should I choose?
The choice in GHRH is quite simple: tetrasubstituted GRF (1-29). This GHRH is also commonly sold as mod grf(1-29), CJC-1295 without DAC, or CJC-1293. Mod grf(1-29) is ideal in that it has an appropriate half-life to support a healthy pulse, and will not cause HGH Bleed.
What about CJC-1295, also known as CJC-1295 with DAC?
This GHRH is to be avoided. To understand the difference, understand that CJC-1295 w/ DAC is similar to mod grf(1-29) with the exception of the addition of the DAC, or Drug Affinity Complex. This addition was designed to increase the half-life of GHRH significantly. The issue with using a GHRH that has such a long half-life is that its constant presence will lead to GH Bleed. As mentioned previously, GH Bleed is undesirable as it leads to reduction in pulse strength of HGH release, a constant release of HGH, and overworks the cells impeding on their ability to communicate as a network.
Which GHRP should I use?
This is where the choice becomes a bit more personal. There are three peptides that are readily available GHRPs to choose from: GHRP-6, GHRP-2, and Ipamorelin.
GHRP-6 has an effect on GH release, increases hunger, causes gastric emptying, and increases cortisol and prolactin.
GHRP-2 has a stronger effect on GH release, does not increase hunger or cause gastric emptying as much as GHRP-6, and increases cortisol and prolactin.
Ipamorelin has a lessened effect on GH release, but in turn has no substantial effect on hunger, gastric emptying, cortisol, or prolactin.
If you are sensitive to, or would like to avoid the increase of either cortisol or prolactin, it would be advisable to choose the more expensive Ipamorelin.
If not, the stronger effect of the GHRP-2/6 would probably be a better choice. GHRP-6 should be chosen if the benefit of increased hunger would correlate with your goals. Elsewise, the increased effect of the GHRP-2 would probably suit you best.
How do I reconstitute the Peptides?
I personally recommend reconstitution with Bacteriostatic water. For instruction on how to reconstitute peptides, please see my other guide: Understanding Reconstitution: A Simple Guide (http://www.swolesource.com/forum/human-growth-hormone-peptides/202-understanding-reconstitution-simple-guide.html)
How are these peptides administered?
Peptides are administered through a subcutaneous injection with an insulin syringe (29g-31g). Subcutaneous (under the skin) injections are performed, most commonly on the abdomen, by pinching an area of fat and inserting the needle at a 45 degree angle (may be done at other angles depending on body fat). Once inserted, it is advisable to aspirate (pull back slightly on the plunger to make sure no blood is present, a sign that you are in a vein). Assuming no blood is present, the peptides can be injected.
More information on injection technique can be found here: (Warning: PDF) (http://www.cc.nih.gov/ccc/patient_education/pepubs/subq.pdf)
How often should I administer the peptides?
This is an entirely personal question, and will vary depending on goals and injection frequency tolerance of a user.
The standard protocol has been (on average) dosing 3 times a day (AM, post-workout (or pre-cardio), and pre-bed).
For those that choose to only administer once a day, pre-bed administration is most advisable.
Once daily dosing is typically utilized for the benefits in rest, rejuvenation and anti-aging.
More frequent dosing is considered much more ideal in terms of fat loss and muscle gain.
The general rule of thumb with frequent administration is to not dose more frequently than every 3 hours, as presented earlier.
Anything to consider when dosing?
You will want to dose on an empty stomach, or at least in the absence of fats and carbohydrates, both of which can blunt the body's release of HGH. You also want to avoid eating for approximately a half hour post administration in order to allow the pulse to reach its peak.
Final Note
Experimentation is key to finding a protocol that works for you. Peptides can be a great addition to any hormonal cycle (where, imo, they really shine) or even run as solo products.
Good luck with your research.
-h2s