GHRH and GHRP explained.

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The secretion of hGH over your lifespan begins to decline in latter years. This can lead to increased central obesity, reduced muscle mass and bone mineral content, as well psychological perception of well being. This age related deficiency is called somatopause. This deficiency is not only related to body composition changes, but it is also responsible for intrinsic diseases that are the leading cause of death after the age of 50. For years this has been treated with recombinant human Growth Hormone. This treatment was effective but left room for improvement. Recombinant hGH lacks the ability to stimulate some naturally occurring profiles that are essential to the secretion of hGH. A better approach to this treatment would be to stimulate the neurocrine system by specifically targeting the pituitary gland.

In the 1960s regulation of hGH had become the primary research within hormone research. During this time some other regulatory factors had come to light, one of those is somatostatin (SS). SS had been identified as capable of blunting hGH secretion. At the time it was thought that SS was the sole regulator of hGH secretion. This did not make much sense to the researchers because it went against their current findings in the clinical setting. After ten years GHRH was identified. GHRH was first identified in humans but not in their brain tissue, it was found in pancreatic islet tumors of those that had acromegaly. Since GHRH is distributed in the body it is called a brain-gut peptide, because it includes another pituitary agent ghrelin. Ghrelin was only discovered in the last decade but the existence was implied in a number of synthetic molecules called GHRP or GH releasing peptide. The first discovery of a GHRP was made in 1977 and is what the current GHRPs were modeled on, with the most recent being formulated, GHRP-2.

GHRP-6 was the first hexapeptide with strong hGH releasing abilities. Currently, in the pharmaceutical world, we understand that hGH is regulated by a complex network of neural and endocrine factors. Two main regulators are GNRH and SS (somatostatin) and one ancillary factor. So even though both GHRH and GHRP stimulate production and attenuate the inhibitory actions of SS, there is a striking synergistic effect when the two are used in conjunction. This results in immediate amplification of hGH secretion.

Growth hormone secretion is a pulsitory effect and this is shown in all species. This pattern is necessary for growth hormones' efficacy. The continued exposure of GH that recombinant hGH induces has been shown to have a less effective physiological response in animals and humans. After all it is the reduction in these pulses, and the eventual disappearance of them altogether, that is responsible for the downfalls of somatopause. Lets take a look at some of the advantages of these receptor specific analogues over RhGH.

* The stimulatory effects of GHRH and GHRP are regulated by the negative feedback loop from the brain to the pituitary. This makes it hard, if not impossible to induce over exposure to hGH.

* Tissue exposure to hGH due to these secretogues are not "square wave" and stimulate a youthful function of this part of the endocrine system and prevents tacphylaxis.

* The stimulatory effect of GHRH and GHRP refreshens the neuroednocrine axis, which is the first part of the system to decline with aging. This opposes the age related failure of this system, thus regulating other parts of the total function such as : Thyroid, adrenal and reproductive systems.


So what does all this mean? It means that not only can these secretogues be more effective than RhGH but they are also safer. Taking one of these alone is not a great idea since you will not get much stimulation form one or the other. For some unknown reasons taking the two together result in a substantial increase of hGH secretion, over one alone. This can be seen in the following graph.

Orange- placebo

Blue and green- GHRP

Yellow- GHRH

Red- GHRH and GHRP used in conjunction.

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Central and peripheral peptides participating in the control of food intake and energy expenditure (neuropeptide Y, leptin, and ghrelin) are also involved in the regulation of GH secretion. Altogether, nutritional status has to be regarded as a major determinant in the regulation of the somatotropin, somatomedin axis in animals and humans. Thus, over- and undernutrition represent two conditions connoted by GH hypersensitivity and GH resistance, respectively. These abnormalities are likely due not only to the lack of negative IGF-I feedback, but also to a primary hypothalamic alteration with increased frequency of growth hormone releasing hormone discharges and decreased somatostatinergic tone.

ScienceDirect - Frontiers in Neuroendocrinology : Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa

So why is this important to know? The presence of insulin will blunt GH secretion, so we know not to eat any carbohydrates or fat before and after the shot. For instance, have you ever ate a large carbohydrate enriched meal and felt very tired afterwards? Yes we all have. When we eat a carbohydrate rich meal, blood sugar levels increase as the carbohydrates are broken down into their base molecules - sugar. As blood sugar levels increase, insulin is released in response. Insulin is a hormone which moves glucose (sugar) from the blood into the muscles and fat cells for storage. This would be counterproductive because we know insulin has the capability to blunt hGH secretion.

The first thing people say when I tell them about these peptides is "don't those make you really hungry?" Well yea it actually does, so much that it's almost weird, i'm hungry within 15 minutes of my shot. This happens because of the stimulation of ghrelin, which happens in the hypothalamic arcuate nucleus, where it stimulates hGH secretion in the anterior pituitary. So basically there is no way around it, anything that does the job well will have some effect, or it will be less effective.

Ghrelin has a few other responsibilities too. It plays a role in neurotrophy, mainly at the hippocampus and is responsible for cognitive adaptation of changing environments, and the learning process. Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, altering nerve-cell connections, and so enhancing learning and memory. This might be why I find it very easy to control my ADHD while on the therapy.

Lets look at what we have so far and see if this will effect our protocol. Your suppose to inject these on an empty stomach, which for me, takes about 2 hours. So by the time you do your shot, its time for the next meal anyway. It is not like the hunger stays with you all day or anything, it goes away as soon as you eat (this is seen in my explanation of ghrelin above). Basically the hunger does not get in the way of my diet and it has actually become a cool way to trigger my hunger at the times I will be eating my biggest meals, except at night.

Although we take these on an empty stomach, we do not want to consume any carbohydrates or fats immediately following the shot either. Your hGH secretion will be rising for about an hour after the shot, if we use the graph in the above post for timing. The other hour of the hGH pulse is spent on the decline. To me disregarding these nutrition rules while implementing such protocol is counterproductive and a waste of money IMHO.

So the rule: On an empty stomach and nothing but PURE protein for at least 45 minutes after shot administration.