I appreciate your thoughts on this topic. Interesting point you bring up here. I've had very noticeable, visible results in size, hardness, and leanness when pinning IGF LR3 2x daily, morning and PWO, several years ago, when I didn't know any better at around 100mcg daily, 4 on, 4 off, for 30 days. Perhaps it was the morning dose that was the effective one. At the same time, I noticed just a ridiculous amount of bloating in the gut a couple of hours after pinning PWO, which put me in a mild hypoglecemic state accompanied with massive hunger. It seems like my system didn't know how to deal with the food or anything else in this state. My gut is still slightly distended, although not grotesquely, which I attribute to excess LR3 floating around with no where to land except my organs --can't prove it, but that is what I suspect.
I also tried the IGF-LR3 / PEG-MGF combo a couple of years ago under the "Flawless Training" guy's protocol with the published "handbook" (and discussed pretty heavily on the boards) with the theory that MGF actually acted like MGF created and replenished cells and IGF would split-out new cells: PEG-MGF on off days 2x weekly, followed by a 2x daily regimen of LR3 at much lower doses (20-40mcg daily). This wasn't such a great idea-- absolutely ridiculous bloating to the point where I looked pregnant. Once again, not such a great idea. I held water like a dam, and got pretty fat pretty fast after discontinuing, which I suspected was due to downregulation of my natural IGF levels.
Then, I've ran PEG-MGF a couple of times by itself a couple of times in the last year, 1mg weekly, split out in 2 x 500mcg on off-days for 4 weeks. I noticed the fullness in the muscles which I attributed to better glycogen uptake, and at the end of week 4, I saw a clear reduction in bodyfat, and came out a couple of pounds heavier on the scale at the same time. No noticeable water retention and bloating -- just nice results.
So, in a way, I wanted to tap into your scientific mind to validate what I have already field-tested empirically.
Now, I'm running GHRP-6 along with the PEG to see if I can round-off the protocol with some anti-aging effects (I've also tried the CJC / GHRP combo and I retained too much water for my liking). So far, one week into it, it is going well, but too early to tell. Lots and lots of bowel movements! My fibre intake is already pretty high, but I like being regular and carrying as little as possible in the gut. The muscles feel full and hard, and the sleep is good.
What would be the effect of a 500mcg dose of GHRP-6 alone on GH, cortisol, and prolactin? Is this much too high of a dose to take before bed? At what point does cortisol production become too high from GHRP-6? Also, how long would cortisol stay elevated?
Too high? Well for some that are sensitive any rise is too high.
But if the normal range is our target then no dose of GHRPs should take you beyond the normal range. ...upper normal yes.
From the point of view of "will 500mcgs of GHRP-6 in a single dose create too much prolactin & cortisol" the answer is NO (as long as the normal range is our guide).
Prolactin rise in response to GHRPs is relatively small and remains constant w/ age.
ACTH & Cortisol rise in response to GHRPs is more pronounced, falls back to baseline or below after 45 minutes or so and does vary with age.
From, Endocrine Response to Growth Hormone Releasing Peptides across Human Life Span, Ezio Ghigo, Growth Hormone Secretagogues in Clinical Practice, Barry B. Bercu CRC 1998:
The stimulatory effect of GHRPs on Prolactin secretion in humans is slight and dose dependant. In fact the rise in PRL after GHRP administration is within normal range of basal PRL. Moreover the PRL response to hexarelin is markedly lower then that recorded after TRH and even after Arginine administration.
Not much. GH Binding protein for the most part is the extracellular portion of a GH-receptor that sloughs off. There level rises and falls with that of the GH ligand. So in GH troughs they are low and during pulses they are high.
All your test did was take a snapshot of a moment in time...the test was probably undertaken when there was no active GH pulse occurring.
An accurate picture of what is going on would involve a series of snapshots over a period of time which should include troughs & pulses.
Just to be clear, so we are taking an educated risk experimenting with ghrh's and ghrp's knowing that they potentially cause cancer and also reduce life expectancy? We seem to be educated people here and we also care for our health considering we control our diets and workout regularly...so why are we doing this? I mean, is the juice worth the squeeze on this one?
This is a stretch, but what if smoking cigarettes added 10lbs of lean muscle a year. Would we all be smokers?
Just to be clear, so we are taking an educated risk experimenting with ghrh's and ghrp's knowing that they potentially cause cancer and also reduce life expectancy? We seem to be educated people here and we also care for our health considering we control our diets and workout regularly...so why are we doing this? I mean, is the juice worth the squeeze on this one?
This is a stretch, but what if smoking cigarettes added 10lbs of lean muscle a year. Would we all be smokers?
Kutch please take what I am about to say seriously and not in jest... in regard to cancer we are taking an educated risk every time we eat.
A strategy of glucose starvation (undertaken to reactivate the full tumor fighting protein P53 response) when you have some forms of cancer may be an effective tumor-fighting strategy. See my post: Post #433
The converse would be the failure to be on a non-ketogenic diet + low calorie diet in the presence of cancer could promote proliferation.
If we want to carry this further we can point to nutrient dense but calorie-restriction (i.e 40%+ below maintenance for an already skinny person) diets as a means to increase life-span and decrease incidences of cancer.
So eating & living increase our risks of getting cancer & reduce our maximum lifespan.
Thank you Roy Walford for your pioneering work in this area. You will always be remembered. Rest in Peace.
Prostate cancers or at least size increases are probably more likely as a result of running body builder doses of steroids.
Hormonal excess is unhealthy. Hormonal balance (in my opinion) is healthy.
As an analogy... it you rock the boat to get the bow to dip to water level you sure will be able to scoop a lot of fish...but there is a price to be paid and that rebound will take you so far above the water you may not be able to get a single fish for a while...and then the worst part is the rocking back and forth until the boat is again balanced out...
Bodybuilders take calculated risks when they use steroids and peptides.
Now they can keep the increase in risks small or they can take on a lot of risk.
In my opinion there is a big difference between always having GH around and having it come and go in a pulse. It doesn't matter if GH is around because of a disease or because of continual administration of synthetic GH....that is IMHO unhealthy.
Why?
Because there is nothing special about that GH ligand (i.e. 191 amino-acid chain). It is not a catalyst or an enzyme...it is nothing in plasma. It is only when it binds to a GH-receptor does stuff happen. Think about a pinball machine. GH is analogous to the ball you set in motion. When/if that ball hits one area all sorts of bells go off, sound bites, points go up, there are vibrations, bonuses maybe, etc. All the ball did was activate things.
As we look into what is going on at the receptor level we find signaling cascades that are activated. These signaling cascades can signal events which may be the communication to proliferate, differentiate or induce apoptosis. The duration of that signaling cascade, the magnitude of that signaling cascade and whether it translocates to the nucleus or not all determine whether, growth, survival or cell-cycle arrest are to occur.
There is a danger in my opinion in significantly disrupting the method of communication the body has chosen. In the case of GH release it starts as signals from the CNS which are triggered by the body's response to events elsewhere, the hypothalamus then responds to those signals (as well as short-loop feedback) in modulating the release of certain hormones such as GHRH & somatostatin. These hormones in turn command the pituitary to release GH from its stores. The somatotrophs (GH releasing cells in this case) in the pituitary "self-organize" a response as they communicated amongst themselves. This network defines the pulsatile response and for the most part a concentrated coordinated secretion of GH is effected.
A concentrated release of GH is a different sort of event then "GH bleed/drip". A concentrated release effects a communication strongly which will lead to activation of GH-receptors in mass.
This is how the body behaves... and when we use GHRH/GHRPs we don't violate that established rhythm.
But when we use GH we are introducing a different form of communication one of which is to shift to a more female-like GH secretion pattern (raised troughs) leading to a shift in manufacture of certain liver enzymes such as the Cytochrome P450 enzyme variants which are responsible for metabolism of steroid/androgens.
Anyway...I don't want to get off track...but the simple point is that I see the use of synthetic GH as much more of a risk then GHRH/GHRP-6 and I also see the supra-pharmacological doses of ALL compounds as riskier then physiological doses (or restoration to youthful levels).
Well, there is SCIENCE behind using T3 or T4 with GH, it just isn't how people portray it. GH doesn't decrease natty thyroid as you say, not at first at least. What it does, as Dat has noted, is modulate the conversion of T4 to T3...making MORE T4 convert to T3. This would make sense, b/c we see that T3 levels increase and T4 levels decrease...this is due to more T4 converting. So what actually occurs is that GH is making your thyroid "work harder" to keep up and produce more T4. It usually can do this with smaller dosages, but with long term use, the body cannot keep up with its T4 production and instead of increased T3, we see that the body sort of "runs out" of T4 to convert. This is when we see a decrease in both T4 and T3, which is the supression people think of. It can vary person by person and in degree considerably. Many people probably don't need any thyroid supplementation at all...and as Dat said, T4 is likely a better option b/c it's T4 that is being converted at a higher rate. What you want to do is get your T4 levels back to normal...not suppress the thyroid with exo T3. This is just my opinion. Also, you should probably get a blood test to see if you need it, instead of just haphazardly dosing thyroid...or at least use only 50mcg of T4 and check body temp daily.
Dat may have a point about the timing. I tried MGf and the only time I felt a good pump or saw any diff was when I administered the night before . But switched to post workout due to all I read about that supposedly being the best time. I did a mg a week for one month no AAS didn't get much
Then, I've ran PEG-MGF a couple of times by itself a couple of times in the last year, 1mg weekly, split out in 2 x 500mcg on off-days for 4 weeks. I noticed the fullness in the muscles which I attributed to better glycogen uptake, and at the end of week 4, I saw a clear reduction in bodyfat, and came out a couple of pounds heavier on the scale at the same time. No noticeable water retention and bloating -- just nice results.
Thank God I don't have anything to sell. I just want to know & understand like everyone else. Since bodybuilders can look in the mirror and report what they see that is the best way to determine if something is working.
Science can then give us the how.
Unfortunately almost everyone has used IGF-1 LR3 PWO so we don't have so much feedback for other protocols.
But on the other hand a lot of people have used peg-MGF (I am assuming it behaves as IGF-1) at times that were not PWO and they report some results.
So we might be on to something. Reminds me of the Hotels dot com TV ad in the U.S. where the guy is putting two types of hotel shampoo in his hair and saying... "its working, its work'n ...they got me" Here's the clip: http://www.videosift.com/video/Ugh-they-got-me-Uugh-It-s-working
Moose069 said:
Now, I'm running GHRP-6 along with the PEG to see if I can round-off the protocol with some anti-aging effects (I've also tried the CJC / GHRP combo and I retained too much water for my liking).
I did as well! I believe that was genuine CJC-1295 that did that to me (2mgs per week w/ 2mgs GHRP-6).
The mod GRF(1-29) w/ GHRP-6 at 1mgs per week, has not had that bloated effect.
Moose069 said:
So far, one week into it, it is going well, but too early to tell. Lots and lots of bowel movements! My fibre intake is already pretty high, but I like being regular and carrying as little as possible in the gut. The muscles feel full and hard, and the sleep is good.
I think people are either really, moderate or not so sensitive to the effect on the bowels. It is a motility action. So anything that will decrease the motility will help.
Imodium is an OTC that slows motility. You may benefit from just half a pill.
Here is a quick note underscoring how nature stops production of IGF-1 in muscle post-exercise and significantly secretes MGF.
There have been animal studies that have examined the impact of muscle overload on IGF-I isoform expression but there has only been one (that I could find) human study in which this has been examined . That study * examined the expression of the MGF (IGF-IEc) and IGF-IEa isoforms before and 2.5 h after a single bout of high-resistance weight-lifting exercise, with the result that MGF was upregulated by 2-865% and the IGF-IEa isoform remained unchanged.
* - Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise, M. Hameed, J Physiol Volume 547, Number 1, 247-254, February 15, 2003
Dat, I am in agreement on the GHRH/GHRP vs GH comment with respect to T4. You are likely right...GHRH/GHRP would probably less often necessitate the usage of T4. Good comment
I have a related question. My wife was given thyroglobulin by her doctors when she was competing in her former country. Of course over time, this caused her body to not produce thyroglobulin. She has absolutely no problem producing T3 and T4. Here in the US she is not able to import thyroglobulin so our doctor has switched her to Armor thyroid, which believe it or not has worked fine. All lab test show TSH, T3/T3 levels to be normal with the medication now. The last blood work was done in December.
Will using CJC 1295/GHRP-6 have any effect on the use of this product? The Armor thyroid is providing 38 mcg levothyroxine (T4) and 9 mcg liothyronine (T3) per grain of thyroid. She takes 1.5 gains/d. Is there some possibility that the body will start producing thyroglobulin again?
So, I'm definitely not pinning PWO, and that's probably why I had good results the last couple of times.
The only question that remains in my mind is how long is the PEG-MGF active when I do pin? 4 hours approximately? I don't want it to interfere with the GHRP-6 actions or vice versa. I'm thinking if there isn't any conclusive findings on how long PEG-MGF is active, I'll just skip the GHRP-6 treatment the evening of the PEG-MGF application.
So, I'm definitely not pinning PWO, and that's probably why I had good results the last couple of times.
The only question that remains in my mind is how long is the PEG-MGF active when I do pin? 4 hours approximately? I don't want it to interfere with the GHRP-6 actions or vice versa. I'm thinking if there isn't any conclusive findings on how long PEG-MGF is active, I'll just skip the GHRP-6 treatment the evening of the PEG-MGF application.
I think that GHRP-6 will, due to its inhibition of somatostatin, help overcome the blunting effect of IGF-1 & the hypothalamic release of GHRH it engenders should remain. (see IGF-1 inhibition below)
In addition the use of testosterone will help overcome the blunting effect of IGF-1. (see Testosterone below)
The MGF peptide.
In the brain ischemia study they "prepare[d] a synthetic, 24 amino acid long MGF C-terminal peptide (NH2-YQPPSTNKNTKSQ(d)R(d)RKGSTFEEHK-NH2). To increase its stability (peptide was found to be rapidly degraded in serum or tissue fluids) the D form of arginine was used for synthesis and the N terminus of the peptide was PEGylated."
They injected in the carotid artery and the protective effect lasted up to 48 hours but that tells us nothing about the half-life of the peptide, just the duration of events it activates.
So I don't really know. I think 4 hours is a good guess.
IGF-1 inhibition
Everyone understands that IGF-1 is synthesized in the liver BUT almost noone knows that it is also synthesized in the brain (hypothalamus) .
The inhibitory effects of IGF-1 on the hypothalamic release of GHRH are well established. However hypothalamic GHRH mRNA levels (i.e. synthesis) are resistant to systemic infusions of IGF-1 but responsive to direct infusion into the brain.
In other words IGF-1 is synthesized in the hypothalamus in response to various events and this inhibits GHRH. However administering IGF-1 or IGF-1 LR3 in the body systemically will have no direct effect on the brain and will not inhibit GHRH & thus GH.
All of that is in the short-term.
The longer-term feedback results in IGF-1 stimulating the synthesis and release of Somatostatin.
IGF-1 also directly inhibits pituitary GH gene transcription. This means that less GH will be made and stored and available for the next pulse.
IGF-1 also inhibits at the pituitary "basal-, cAMP-, protein kinase C-, GHRH- and TRH-induced GH release." *
"IGF-1 is...far less effective in inhibiting GH release than Somatostatin and [thus] may [in actual fact] only [directly] inhibit GH release from a subpopulation of GH cells that are not responsive to Somatostatin inhibition". *
So even if you block Somatostatin (w/ GHRP-6, etc.) then IGF-1 will still act (to a weaker degree) directly on those cells and inhibit GH-release. This would in total amount to a blunting rather then outright arresting.
* Growth Hormone, Stephen Harvey, CRC Press 1995
Testosterone
Rexanator originally referred me to Testosterone Blunts Feedback Inhibition of Growth Hormone Secretion by Experimentally Elevated Insulin-Like Growth Factor-I Concentration, Johannes D. Veldhuis, Stacey M. Anderson, Ali Iranmanesh and Cyril Y. Bowers, The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 3 1613-1617, 2005, where they found:
"...supplementation of a high dose of Te in middle-aged and older men attenuates IGF-I feedback-dependent inhibition of nadir and peak GH secretion."
The results of this study were confirmed in a recent study published this year:
Testosterone Supplementation in Older Men Restrains Insulin-Like Growth Factor’s Dose-Dependent Feedback Inhibition of Pulsatile Growth Hormone Secretion, Johannes D. Veldhuis, Daniel M. Keenan, Joy N. Bailey, Adenborduin Adeniji, John M. Miles, Remberto Paulo, Mihaela Cosma and Cacia Soares-Welch, The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 1 246-254, 2009
Background: Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia.
Hypothesis: Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I.
Subjects: Twenty-four healthy men (ages, 50 to 75 yr; body mass index, 24 to 30 kg/m2) participated in the study.
Methods: We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m2.
Analysis: Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted.
Results: Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P = 0.025), burst number (P = 0.005), interpulse variability (P = 0.032), and basal GH secretion (P = 0.009); and 3) increased secretory pattern regularity (P = 0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P = 0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I’s inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity.
Conclusion:The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.
Will using CJC 1295/GHRP-6 have any effect on the use of this product? The Armor thyroid is providing 38 mcg levothyroxine (T4) and 9 mcg liothyronine (T3) per grain of thyroid. She takes 1.5 gains/d. Is there some possibility that the body will start producing thyroglobulin again?
If CJC/GHRPs were having a negative effect it is likely she would have experienced symptoms by now. If it did produce a negative effect simply stopping CJC/GHRP would probably remedy the problem.
As for a positive effect I wouldn't venture a guess other then to say it is unlikely that CJC/GHRP alone would remedy the problem.
In an interesting recent study (quoted below) we discover that an IGF-1 receptor isn't even needed post-exercise to induce the intracellular signals that lead to growth.
The IGF-1 receptor, analogous to the ignition in a car, is bypassed and the intracellular growth pathways are "hot-wire" started by the mechanical workout.
So if the IGF-1 receptor isn't needed then the key, IGF-1 seems like a waste...maybe (at least in the post-workout environment)
So how are the growth pathways activated without IGF-1/IGF-1 receptor?
From Muscle growth: no IGFs, ands, or buts, D. Lee Hamilton and Keith Baar, J Physiol 586.1 (2008) pp 5–6
If growth factors aren’t required for the activation of mTOR or muscle growth, how is the mechanical signal transduced to a chemical signal that promotes hypertrophy (Fig. 1)? One possibility is that mechanical loading activates phospholipase D resulting in the activation of mTOR and muscle hypertrophy (Hornberger et al. 2006). However, this doesn’t explain the activation of PKB/akt that occurs following resistance exercise. Another possibility is that mechanical loading overcomes the requirement for the growth factor receptor by altering the normal turnover of signalling molecules at the membrane. In this way, both PKB/akt and mTOR can be activated in the absence of growth factors. While growth factors and hormones are important developmentally in determining the size of our bodies, it is clear from the work of Spangenburg et al. that the primary stimulus for adult skeletal muscle hypertrophy is the mechanical environment.
Figure 1. Schematic diagram of the signalling pathway associated with skeletal muscle hypertrophy Insulin and growth factors (GF) signal through the insulin receptor and its substrate (IRS1), whereas resistance exercise bypasses this receptor and activates protein kinase B (PKB)/akt independently of the insulin receptor. In both cases, the mammalian target of rapamycin (mTOR) is activated leading to protein synthesis via the protooncogene myc, the liberation of eukaryotic initiation factor (eIF) 4E from its repressor the eIF4E binding protein (4E-BP), and the activation of the 70 kDa ribosomal S6 kinase (S6K1).
From the study:
A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy, Espen E. Spangenburg, J Physiol 586.1 (2008) pp 283–291
Discussion
These data represent the first demonstration that the IGF-I receptor is not necessary for the induction of skeletalmuscle growth in response to mechanical loading. The transgenic mice employed in these studies express a mutated IGF-I receptor specifically in skeletal muscle that acts in a dominant negative fashion to prevent activation of the IGF-1R in response to binding of endogenous or exogenous IGF-I. Thus, if up-regulation of IGF-I and receptor activation are critical factors for load-induced skeletalmuscle hypertrophy, then mice deficient in IGF-IR mediated signalling should not respond to functional overload with an increase in muscle mass. However, these data demonstrate quite clearly that signalling through the IGF-IR is not necessary for load-induced muscle hypertrophy since the MKR mice retain the capacity to induce muscle growth in response to functional overload. Furthermore, we demonstrate that components of the Akt–mTOR signalling pathway, thought to be critical for the induction of muscle growth, were activated equally by the overload stimulus in both the WT and MKR mice. Thus, these data suggest that although exogenous IGF-I can induce muscle hypertrophy, the production of endogenous IGF-I by skeletal muscle and activation of the IGF-IR are not necessary for the activation of Akt-mediated signalling or the induction of muscle growth in response to mechanical load.
Numerous publications have demonstrated that the addition of exogenous IGF-I can induce muscle hypertrophy (Adams & McCue, 1998) and in some cases rescue muscle mass (Barton-Davis et al. 1998; Chakravarthy et al. 2000; Musaro et al. 2001). In response to an increase in mechanical load, skeletal muscles increase IGF-I mRNA and protein expression (DeVol et al. 1990; Adams & Haddad, 1996), which has led investigators to conclude that IGF-I is a critical factor involved in skeletal muscle hypertrophy. Unfortunately, this hypothesis has been difficult to test.
...
Our data do not support the current thinking with regard to how increased mechanical loading induces skeletal muscle hypertrophy, which proposes that mechanical loading (i.e. resistance exercise) results in enhanced IGF-I mRNA and protein production by the skeletal muscle resulting in an induction of muscle growth through the activation/proliferation of satellite cells and/or increase of protein synthesis through downstream activation of PI3K–AKt–mTOR and Raf–MEK–ERK signalling pathways (for review see Adams, 2002). Clearly, the MKR mice had no limitation in their ability to induce muscle growth, and in fact the signalling pathway by which IGF-I is thought to mediate the increase in protein synthesis, i.e. Akt–mTOR, was fully activated with the increase in load. Thus, IGF-I does not appear to be a limiting factor in the induction of muscle hypertrophy with increased mechanical loading, and other possible upstream signals should be considered. In fact, a few recent studies have suggested that the effects of mechanical loading may be mediated through other factors such as phospholipase-D to activate mTOR and its downstream pathways (Hornberger et al. 2006) and hepatocyte growth factor for the induction of satellite cell proliferation (Tatsumi et al. 2006).
...
It should be pointed out that these data do not question the ability of IGF-I to induce growth or to be used in a therapeutic sense, but only demonstrate that IGF-I is not necessary for the activation of Akt–mTOR-mediated pathways or muscle hypertrophy during mechanical loading and is not critical to induce growth. Exogenous IGF-I, whether delivered systemically or through genetic means, clearly has the ability to induce muscle hypertrophy (Adams & McCue, 1998; Barton-Davis et al. 1998; Schertzer & Lynch, 2006), and has potential value in treating muscle degenerative diseases and sarcopenia.
In conclusion, utilizing a transgenic mouse model in which skeletal muscles cannot respond to IGF-I or insulin due to the over-expression of a mutated IGF1R, we demonstrate that IGF-I receptor-mediated signalling is not necessary for the induction of skeletal muscle hypertrophy in adult mice following a chronic increase in mechanical loading. Thus, unless IGF-I can work through an unknown alternative receptor, it does not appear that IGF-I receptor is part of the upstream mechanism that activates Akt/mTOR signalling pathways during increased mechanical load. However, one must consider the possibility that mutation in the IGF-I receptor in the MKR mice results in an unexpected compensation that is allowing these mice to still respond to mechanical loading. Clearly, these experiments demonstrate the need for additional work to identify the upstream mechanisms responsible for activation of Akt-mediated signalling in response to loading and other growth stimuli.
What does GH contribute to anabolism besides creating IGF-1?
What does GH (by itself) do?
Acute growth hormone effects on amino acid and lipid metabolism, KC Copeland and KS Nair, Journal of Clinical Endocrinology & Metabolism, 1994 Vol 78, 1040-1047
Abstract
The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12- 20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects...
Discussion
+The most impressive finding of our study is that an acute infusion of GH is associated with a prompt inhibition in leucine oxidation, a metabolic action independent of other hormonal changes.This observation, in the context of our study design, is of particular importance since previous studies examining the protein anabolic actions of GH may not have controlled for anabolic effects mediated by a secondary increase in insulin secretion (29-31). In our study, insulin levels were identical in control and GH treatment groups. This reduction in leucine oxidation was not associated with an increase in plasma leucine concentrations, most likely because the
+GH infusion also was associated with an increase in whole body protein synthesis. This observation of an acute increase in the rate of whole body protein synthesis supports the findings of Horber and Haymond (32), who also observed a stimulation of whole body protein synthesis in normal subjects and corticosteroid-treated subjects given GH chronically.
=GH itself seems to be responsible for the observed protein anabolic effects (inhibition of amino acid oxidation and stimulation of whole body protein synthesis) since insulin, glucagon, cortisol, IGF-I, catecholamine, and glucose concentrations were not different between control and treatment groups. It should be noted, however, that the GH infusion was associated with an increase in glycerol concentrations, indicative of lipolysis. Therefore, it is possible that the observed protein anabolic effects may have been mediated by the GH-induced release in lipid substrates (glycerol, free fatty acids, or P-hydroxybutyrate).
-Our data also suggest that the acute GH-induced increase in whole body protein synthesis occurs primarily in nonskeletal muscle tissues, as indicated by the directional changes in leucine and phenylalanine disappearance rates across the leg. The magnitude of this discordance between whole body and skeletal muscle may be physiologically important (Table 4). Given the assumptions noted in Table 4 (33) and the conditions of the protocol design,
=GH treatment resulted in an hourly net accretion of 32 mg whole body protein
-but an hourly loss of 77 mg skeletal muscle protein (relative to baseline values). Assuming continued unperturbed biological action of GH (including confounding effects by IGF-I or insulin), this would translate to an average loss of 1.8 g skeletal muscle protein each day. It is well known, however, that GH treatment invariably is followed some 6-8 h later by a significant increase in blood IGF-I (34), which may stimulate skeletal muscle protein anabolism.
This observed relative increase in whole body protein synthesis without concomitant increase in muscle protein synthesis is consistent with the report of Yarasheski et al. (16), who observed no stimulation of muscle protein synthesis during chronic administration of GH when combined with exercise. By contrast, Fryburg et al. (15, 35) demonstrated that GH infused directly into the brachial artery stimulates protein synthesis. This increase in muscle protein synthesis occurred only after a longer exposure to GH than the current study. In addition, in that study an increase in blood flow was observed, whereas in our study the systemic administration of GH was not associated with an increase in blood flow in the leg. Recently, these same investigators reported data on regional effects after a systemic infusion of GH, using a design similar to ours but without a concomitant infusion of somatostatin (36). They observed acute increases in forearm blood flow and amino acid uptake across the arm after GH, without evidence of increased protein synthesis in the whole body. However, increases in both insulin and IGFI concentrations were induced by the GH infusion, which may account for some of the differences observed between their studies and ours (36).
=We believe it is possible that in our study, GH stimulated fast turning-over proteins in organs such as gut and liver, which may have rendered muscle less accessible to amino acids for protein synthesis. An alternative explanation is that the period of GH administration was too short to stimulate local productions of IGF-I in muscle, which may have caused an increased rate of muscle protein synthesis. Recent studies, however, have not shown any stimulation of muscle protein synthesis by IGF-I in humans (37, 38).
= We suspect that the increase in muscle mass observed in GH-treated adults (5- 8) represents a chronic effect on inhibited proteolysis, mediated by IGF-I.
MY NOTE: Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. So IGF-1 inhibits protein breakdown.
+The current study also confirms the lipolytic actions of GH (39). This finding was surprising, considering the relatively high circulating concentrations of insulin in our study, and suggests that under proper experimental conditions, the potent antilipolytic effects of insulin (at the replacement doses chosen) can be overcome by rather modest doses of GH.
These data are consistent with numerous reports demonstrating a reduction in body fat both in GH-deficient (4, 5) or normal (2) subjects treated with GH and in subjects with acromegaly (9, 10). In conclusion, this report confirms the leucine-sparing action of GH in the whole body but provides no evidence for an acute stimulation of muscle protein synthesis. It does not exclude an effect of GH in stimulating protein synthesis if infused directly into a limb, or a chronic anabolic effect on skeletal muscle via inhibited proteolysis, either directly or mediated through IGF-I or insulin. These data also suggest that the acute protein anabolic actions of GH may be nonhomogeneous in muscle and nonmuscle tissue.
If CJC/GHRPs were having a negative effect it is likely she would have experienced symptoms by now. If it did produce a negative effect simply stopping CJC/GHRP would probably remedy the problem.
As for a positive effect I wouldn't venture a guess other then to say it is unlikely that CJC/GHRP alone would remedy the problem.
Thanks anyway! It will be December before her next scheduled blood work. However, I feel like you that if there was going to be a change she would have felt it by now.
I am looking to get a raise in GH levels. And I would choose GHRP-6 (wich I already use) with CJC-1295.
But the problem is CJC-1295 isn't avilable for purchase here in Hungary
What other GH can I use to get the same boost in GH-levels?
Preferably something wich is isn't more expensive.
I am looking to get a raise in GH levels. And I would choose GHRP-6 (wich I already use) with CJC-1295.
But the problem is CJC-1295 isn't avilable for purchase here in Hungary
What other GH can I use to get the same boost in GH-levels?
Preferably something wich is isn't more expensive.
I have read this entire thread with great interest. I am very impressed with your knowledge and your ability to convey information.
As a mom of 5 and martial artist, I initially began research IGF-1R3 to aid in muscle recovery from difficult classes. I am 43 and don’t recover as quickly as my kids! Lol I am also interested in the effects of anti-aging and read those articles with great interest. It seems initially HGH was the anti-aging drug of choice but now GHRP and CJC-1295 can replace HGH at a much lower cost with many of the same benefits. Correct?
However, after reading *** So women should always include a GHRP (GHRP-6, GHRP-2, Hexarelin, Ipamorelin) in their therapy. GHRH (mod GRF(1-29), Sermorelin, CJC-1295) by itself will be inhibited in its action on GH release by the sex hormone estrogen.****
I am curious if in your research you have come across the effects of GHRH/GHRP’s effect on progesterone. Being premenopausal my hormones fluctuate greatly and I would like to know if this would aid in leveling them out somewhat.
Thank you for your generous gift of time over the past couple of years! I have learned a great deal from you.
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I just want to know & understand like everyone else. Since bodybuilders can look in the mirror and report what they see that is the best way to determine if something is working.
