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

DatBtrue said:

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.

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I'm by no means any expert in this area, but I believe that the 24hour urinary analysis of GH that Rhein labs does now ( just started doing this like a few months ago - It is that cutting edge) is probably one of, if not the best way to accurately assess GH production.

If not, it is reasonably easy and not too expensive at 90 bucks. (Beats a GH stim test LOL)

Thanks for the educating post about height growth

But I'm still not sure of what peptide is best for possible height growth?
HGH? CJC-1295? GHRP-6? HGH is used in treatment but is the other two just as good?

I'm barely 5'4" so some help here would make me a happy man.


-Deio

A complete understanding of IGF-1 & its potential influence on cancer & longevity

anhuka said:

thankx for clarifying and for the help DatBtrue

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Here is a VERY current and VERY, VERY good way to really understand this area. It is a series of illustrations from Medscape.

Each figure & explanation helps us understand BUT figure 3 I think really helps us understand "how IGF-1 can increase cancers".

I encourage everyone to read this because you learn so much in just a short space. Don't be concerned if the intracellular discussion from figure 2 is a bit complex. It is enough for you to get the essence of it. The other figures & explanations are highly readable.

If you read this post fully you become very knowledgeable.

The source is Medscape taken from: Nat Rev Cancer 4(7):505-518, 2004. © 2004 Nature Publishing Group

Figure 1. Regulation of circulating and tissue levels of insulin-like growth factors. Most circulating insulin-like growth factors are produced in the liver. Hepatic IGF1 production is subject to complex regulation by hormonal and nutritional factors. Growth hormone (GH), which is produced in the pituitary gland under control of the hypothalamic factors growth-hormone-releasing hormone (GHRH) and somatostatin (SMS), is a key stimulator of IGF1 production. Various IGF-binding proteins (IGFBPs) are also produced in the liver. In IGF-responsive tissues, the ligands IGF1 and IGF2 as well as IGFBPs can be delivered through the circulation from the liver (an 'endocrine' source), but IGFs and IGFBPs can also be locally produced through autocrine or paracrine mechanisms. These mechanisms often involve interactions between stromal- and epithelial-cell subpopulations.

Figure 2. Overview of insulin-like growth factor 1 receptor activation and downstream signalling. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase cell-surface receptor that binds either IGF1 or IGF2. The local bioavailability of ligands is subject to complex physiological regulation and is probably abnormally high in many cancers. Ligands can be delivered from remote sites of production through the circulation or be locally produced. IGF-binding proteins (IGFBPs) and IGFBP proteases have key roles in regulating ligand bioavailability. IGFBPs prolong the half-life of IGFs, which has the potential to increase IGF1R activation. On the other hand, these proteins have affinity for IGFs comparable to IGF1R and there is competition between IGFBPs and IGF1R for available ligands in tissue microenvironments. This provides a basis for the inhibitory roles of IGFBPs on IGF1 signalling observed in many situations. There is evidence that certain IGFBPs also have direct, IGF-independent growth-regulatory actions.

The IGF2R binds IGF2, but has no tyrosine kinase domain and appears to act as a negative influence on proliferation by reducing the amount of IGF2 available for binding to IGF1R. Certain IGFBP proteases (often produced by neoplastic cells) that cleave IGFBPs can release free ligand and thereby increase IGF1R activation. Following ligand binding to IGF1R, its tyrosine kinase activity is activated, and this stimulates signalling through intracellular networks that regulate cell proliferation and cell survival. Key downstream networks include the PI3K-AKT-TOR system and the RAF-MAPK systems. Activation of these pathways stimulates proliferation and inhibits apoptosis. This figure simplifies complex interacting regulatory networks. For many cell types, the key effects of signalling downstream to AKT relate to regulation of cell survival and mRNA translation, while the principal effect of signalling downstream to RAS involves regulation of cellular proliferation. 4EBP1, eukaryotic translation initiation factor 4E binding protein 1; eIF4E, eukaryotic translation initiation factor 4E; ERK, extracellular signal-regulated kinase; GRB2, growth-factor-receptor-bound protein 2; IRS1, insulin-receptor substrate 1; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; PI3K, phosphatidylinositol 3-kinase; PIP, phosphatidylinositol; PTEN, phosphatase and tensin homologue; S6K, S6 kinase; SHC, SRC-homology-2-domain transforming protein; SHP2, phosphatidylinositol 3-kinase regulatory subunit; SRF, serum response factor; TOR, target of rapamycin.

Figure 3. Model of the influence of insulin-like growth factor 1 signalling on the stepwise accumulation of somatic-cell genetic damage in carcinogenesis. The model of stepwise accumulation of genetic damage leading to carcinogenesis can be extended to include influences of insulin-like growth factor 1 (IGF1) signalling. These include favouring cellular proliferation over arrest and cellular survival over apoptosis. This model provides a preliminary biological framework to account for the observed association of higher levels of IGF1, or IGF1 receptor (IGF1R) activation, with cancer risk in epidemiological and laboratory studies. The model predicts that stepwise accumulation of genetic damage is facilitated in individuals with higher IGF1 levels because in these individuals there is a slightly higher rate of cell division (increasing the risk of errors) and, perhaps more importantly, because the probability of appropriate apoptosis of cells with a small number of 'hits' would be slightly reduced in a microenvironment with higher levels of IGF1R activation. The figure greatly exaggerates the magnitude of the hypothesized differences between 'high IGF' and 'low IGF' individuals in proliferation and apoptosis for purposes of illustration. Very small differences in these parameters, if applied to the very large renewing cell populations of organs such as the colon over a timespan of decades could influence the probability of emergence of a fully transformed clone. Colours indicate the following: yellow, normal cells; pale blue, cells containing one mutation or hit; dark blue, cells containing two mutations or hits; purple, apoptotic cells.

Figure 4. Insulin-like growth factor 1 receptor targeting: therapeutic strategies. Work is underway by many groups to develop pharmacological strategies to reduce signalling at and downstream of the insulin-like growth factor 1 receptor (IGF1R), in the hope that this will lead to compounds that are useful in cancer treatment. Approaches that will soon be tested clinically following demonstration of antineoplastic activity in laboratory studies include the use of blocking antibodies directed against the extracellular portion of the receptor and small-molecule tyrosine kinase inhibitors with specificity for IGF1R. Small interfering RNA (siRNA) and antisense strategies to reduce receptor expression, as well as transfection of altered or truncated IGF1R proteins that act in a dominant-negative fashion to interfere with receptor function are additional approaches that have been effective in laboratory studies. There is also great interest in therapeutic strategies that target signalling pathways downstream of IGF1R. Important examples include AKT inhibitors, and TOR inhibitors such as rapamycin and its analogues. IRS1, insulin-receptor substrate 1; PI3K, phosphatidylinositol 3-kinase; TOR, target of rapamycin.

Figure 5. Why is life expectancy increased when insulin-like growth factor 1 levels are reduced? Experimental results provide convincing evidence that in several experimental organisms, decreased insulin-like growth factor 1 (IGF1) signalling is associated with increased lifespan, even though in cell-culture systems reduced IGF1-receptor (IGF1R) activation increases the likelihood of cell death. A model to account for the increased lifespan associated with reduced IGF1 signalling is related to the classic 'rate of living' hypothesis. It is plausible that the process of ageing is related to the number of cell divisions since conception (although other factors are also involved). If the rate of cell turnover increases with higher levels of activation of IGF1R or related receptors, then at any fixed chronological age, there will have been more cell divisions in the ancestry of IGF-responsive cells of individuals with higher levels of receptor activation, compared with individuals with lower levels of activation. By the measure of 'number of cell divisions since conception', at an arbitrary number of years since conception, the individual on the right has aged faster than the individual on the left. If the process of ageing proceeds at least in part as a function of the number of cell divisions since conception, rather than as a function of elapsed time since conception, the individual on the left would live longer.

Dat, do you need to use T3 or T4 when you take GHRP-6, as you do when you take exo GH, or no?

BadGenCD said:

Dat, do you need to use T3 or T4 when you take GHRP-6, as you do when you take exo GH, or no?

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Hey Bad, I'm not Dat LOL, but

I would think as long as your FreeT3 and T4 numbers showed up as mid-range or higher, indicating no need for thyroid hormone replacement, there wouldn't be any need to use it along with your GHRT protocol of GHRH + GHRP.

Meaning the GH booster protocol is for life, or at least the current future, as an anti-aging regiment, and the only additional hormones you need to take are ones that showed up as deficient on a hormone panel.

After all, even if adding in a grain or so might enhance fat loss, etc., if there is no need to, why add in another variable to the mix?

Perhaps possibly DHEA would be the one exception in this area - DHEA might be a good tool to add to the protocol.

But as always, I am interested in Dat's opinions here of course.

Not really what i meant WiseGuy. I know many people say exo GH supresses thyroid output, but does GHRP-6 do the same thing? Does it affect the thyroid? That's what I meant

BadGenCD said:

Dat, do you need to use T3 or T4 when you take GHRP-6, as you do when you take exo GH, or no?

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You don't need it for either GH or the GH releasers.



Keep in mind that most studies focus on people with under-performing thyroids so physiological supplementation has the effect of restoring GH release, while pharmacological doses do not illicit supranormal GH concentrations.

T3 may inhibit GHRH-induced GH release at the pituitary (multiple mechanisms) while T4 shouldn't have an inhibitory effect (i.e. it doesn't effect somatostatin).

So my opinion is that a normal person does not need thyroid supplementation w/ GH or GH releasers. That T3 supplementation may do more harm then good. If you feel the need to supplement with a thyroid hormone T4 would seem to provide more benefit.

IGF-1 & MGF together again

Original post was deleted because I made conclusions based on an abstract of a study. When I read the full study my conclusions changed substantially.

The replacement post is now post #757 below.

DatBtrue said:

Sure it can and cancer as well. To the extent that GH elevates systemic IGF-1 levels or contributes to local IGF-1 in the prostate we have this potentiality ...organ growth ...contributions to cancer risk.

Insulin-like growth factor-I (IGF-I) stimulates proliferation, decreases apoptosis, and has been implicated in cancer development by in vitro and in vivo studies (1-3). Prospective studies have shown elevated levels of circulating IGF-I to be associated with several cancer types, including prostate cancer (4-6)
...
In addition, the GHR gene is expressed in normal and neoplastic prostate epithelium (15), and increased GHR expression seems to be required for the progression of benign prostate intraepithelial neoplasia to prostate cancer (14) - Haplotype-Based Analysis of Common Variation in the Growth Hormone Receptor Gene and Prostate Cancer Risk , James D. McKay, Cancer Epidemiology Biomarkers & Prevention 16, 169, January 1, 2007

1- LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127–37.

2 - Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000;92:1472–89.

3 - Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995;16:3–34.

4 - Shi R, Berkel HJ, Yu H. Insulin-like growth factor-I and prostate cancer: a meta-analysis. Br J Cancer 2001;85:991–6.

5 - Chan JM, Stampfer MJ, Ma J, et al. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst 2002;94:1099–106.

6 - Stattin P, Rinaldi S, Biessy C, Stenman UH, Hallmans G, Kaaks R. High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. J Clin Oncol 2004;22:3104–12.

14 - Wang Z, Prins GS, Coschigano KT, et al. Disruption of growth hormone signaling retards early stages of prostate carcinogenesis in the C3(1)/T antigen mouse. Endocrinology 2005;146:5188–96.

15 - Weiss-Messer E, Merom O, Adi A, et al. Growth hormone (GH) receptors in prostate cancer: gene expression in human tissues and cell lines and characterization, GH signaling and androgen receptor regulation in LNCaP cells. Mol Cell Endocrinol 2004;220:109–23


​

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So cancer survivors should stay far away from IGF?

Curlytop said:

So cancer survivors should stay far away from IGF?

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In my opinion yes.

DatBtrue said:

In my opinion yes.

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that sucks.....

Thank you very much sir!

DatBtrue said:

You don't need it for either GH or the GH releasers.

"GH increases circulating concentrations of T3 while decresing those of T4. ...GH is not influencing the secretion of T3 and T4 but but rather influencing peripheral 5- and/or 5' -monodeiodinase activity and the metabolism of the thyroid hormones and hence the conversion of T4 to T3 (the active form of the hormone)." - Growth Hormone, Stephen Harvey, CRC 1995, p.424​

"Growth hormone treatment reduces T4 secretion and affects the peripheral metabolism of thyroid hormones resulting in an increase of T3..." - The effect of growth hormone on the plasma levels of T4, free-T4, T3, reverse T3 and TBG in hypopituitary patients, G. Gács, Acta Endocrinologica, Vol 96, Issue 4, 475-479​

Keep in mind that most studies focus on people with under-performing thyroids so physiological supplementation has the effect of restoring GH release, while pharmacological doses do not illicit supranormal GH concentrations.

T3 may inhibit GHRH-induced GH release at the pituitary (multiple mechanisms) while T4 shouldn't have an inhibitory effect (i.e. it doesn't effect somatostatin).

So my opinion is that a normal person does not need thyroid supplementation w/ GH or GH releasers. That T3 supplementation may do more harm then good. If you feel the need to supplement with a thyroid hormone T4 would seem to provide more benefit.

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DatBtrue said:

You don't need it for either GH or the GH releasers.

"GH increases circulating concentrations of T3 while decresing those of T4. ...GH is not influencing the secretion of T3 and T4 but but rather influencing peripheral 5- and/or 5' -monodeiodinase activity and the metabolism of the thyroid hormones and hence the conversion of T4 to T3 (the active form of the hormone)." - Growth Hormone, Stephen Harvey, CRC 1995, p.424​

"Growth hormone treatment reduces T4 secretion and affects the peripheral metabolism of thyroid hormones resulting in an increase of T3..." - The effect of growth hormone on the plasma levels of T4, free-T4, T3, reverse T3 and TBG in hypopituitary patients, G. Gács, Acta Endocrinologica, Vol 96, Issue 4, 475-479​

Keep in mind that most studies focus on people with under-performing thyroids so physiological supplementation has the effect of restoring GH release, while pharmacological doses do not illicit supranormal GH concentrations.

T3 may inhibit GHRH-induced GH release at the pituitary (multiple mechanisms) while T4 shouldn't have an inhibitory effect (i.e. it doesn't effect somatostatin).

So my opinion is that a normal person does not need thyroid supplementation w/ GH or GH releasers. That T3 supplementation may do more harm then good. If you feel the need to supplement with a thyroid hormone T4 would seem to provide more benefit.

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That just saved me on a t3 order. I keep hearing from random people that they take 25mcg of T3 on Gh for 2 reasons

1.) it can decrease natty thyroid levels
2.) T3 at 25mcg can help with protein synthesis.

Again I dont listen to anything without science behind it, so im glad you posted this.

POOF


(inside joke)



I'm really getting a lot out of this thread. Good work DatBeTrue. My SO wants to research melanotan... I might start researching GHRP-6 and CJC-1295. I think we could combine our efforts and work through a local research company for everything. I stayed up reading this thread last night until 3am. And I'm still nowhere near 25% through it. eep!



POOF

Curlytop said:

that sucks.....

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Certain cancers don't wait for systemic GH or GHRH or IGF-1 to come their way. Instead they hijack the machinery to make those growth factors locally. When they do this they can metastasize and break through natural boundaries.

Specially constructed and properly targeted antogonists for GHRH, for GH, for IGF-1 are proving to be experimentally sucessfull in both stopping these cancers from growing and in making them shrink.

When coupled with various forms of chemo often total remission ensues w/ the result of no identifiable cancer remaining.

This cutting edge therapy has the advantage of being potentially effective in hard to target cancers such as lung & brain (these antagonists cross the blood brain barrier) and have proven in clinical trials very successful in breast cancer and prostate cancer.

The key being to create delivery vehicles that selectively reach & target cancerous tissue.

IGF-1 & MGF timing

Moose069 said:

Thanks DAT.

So, just to make sure I'm clear, PEG-MGF should be used to promote the myotube formation stimulated by the expression of IGF-1Ea approx. 2 days after a particular muscle group is damaged / exercised? In other words, if you hit your chest two days ago, the PEG-MGF administration today will assist in myotube formation of the chest muscles? Also, this process will last around 4 hours or so?

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I don't know.

Its okay not to know.

I was researching Fibroblast growth factor (FGF). There are several forms. One form seems to be capable of acting in the same manner as Mechano Growth Factor (MGF).

The advantage of FGF would be that unlike MGF, there are receptors for it so exogenously administered peptide could bind to a cell and effect proliferation.

Anyway the key point was that proliferation and differentiation are two sides of the same coin. To stop proliferation you induce differentiation. To promote proliferation you arrest differentiation.

This seems to be the case for all cells. For instance fat cells proliferate. But Octanoate stops proliferation by inducing differentiation. Thus a reduction in visceral fat (given the correct accompanying protocol)

So if we keep this in mind and look at muscle we want to induce proliferation for as long as possible before inducing differentiation. Why? Because if you differentiate too early you have ended the potential to early.

In one study they used FGF to proliferate a cell and they were able to do this for 100+ straight days.

What are we talking about? Lets look at an abstract that looks at these growth factors.


So while all of this is interesting it does not specifically tell bodybuilders how to do things.

Lets see if there is anything we can pull from this.

IGF-1 (if there is no other proliferating growth factor active (such as MGF or FGF) is capable of mild proliferation but strong differentiation activity.

Does IGF-1 interfere with MGF?

From the full study which gives a more complete picture then the abstract:


The presence of TGF-beta was required before the FGF & IGF-1 combo resulted in proliferation instead of differentiation. TGF-beta is present naturally at the time of injury, but "if the TGF-beta that is released from platelets immediately following injury is depleted, leaving only IGF and possibly FGF, satellite cells could be expected to differentiate into myotubes" rather then proliferate.

IF MGF behaves as FGF, then from the study it is only the presence of TGF-beta that would allow MGF to continue proliferating in the presence of IGF-1. When TGF-beta is depleted at the site, then the presence of IGF-1 will override MGF's proliferation activity and instead differentiation will occur.

What I have always been concerned about was IGF-1 stopping MGFs actions. A full read of the study indicates that this is probably a legitimate concern.

So on a practical level it actually may be better to avoid administering IGF-1 (or IGF-1 masquerading as peg-MGF) in the environment where your body creates & utilizes MGF...that is post-weightlifting.

I had been thinking about this IGF-1 LR3 timing before and had thought that post-workout might not be the best time to administer it. This study gives some validity to my previous thoughts.

So how long to wait?

I don't know. Beyond two days would be overkill.

Maybe larger doses of IGF-1 more infrequently is the way to go.

If not perhaps at least waiting till the next day post-workout to administer IGF-1 LR3 is a practical way to go.

One other thought occurs. Perhaps people (myself included in the past) realized very little from IGF-1 LR3 because it was administered post-workout. Perhaps this is the worst time or at least a waste of time, to administer IGF-1 LR3.

And since I am throwing out a bunch of maybes, here's one more...

Maybe Peg-MGF (which acts as IGF-1) is partially more effective anecdotally because people are not administering post-workout.

DatBtrue said:

In my opinion yes.

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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?

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.

fourthgen said:

That just saved me on a t3 order. I keep hearing from random people that they take 25mcg of T3 on Gh for 2 reasons

1.) it can decrease natty thyroid levels
2.) T3 at 25mcg can help with protein synthesis.

Again I dont listen to anything without science behind it, so im glad you posted this.

Click to expand...

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

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?