Those that use IGF1 LR3 preWO and MGF pwo

[123cctv]

truly don't believe that any protocol could yeild better gains.

Data is generally fact. Belief on the other hand? Well, we're not discussing belief here are we?

Most understand there are better times than others to administer a substance. Take GH for instance, I can show you optimal times of admin. Further, based on common sense questions I gave you above, it might occur there are better times to admin for optimal response/gains. For instance, take this question -

4. When are binding protiens which inhibit the peptides anabolic effects at their lowest?

Is the answer to this question, Pre WO? Course not. Thus if so, then why would any one admin it when its effects (anabolic ) will be blunted? I asked another question -

3. What if one peptide cancels out the other?

You're aware IGF cancels out MGF expression? It does. But here's the biggest catch of this mess - exactly when does MGF expression (proliferation) occur? When muscles are torn/damaged, i..e a WO. By admin'ing IGF pre WO you have actually assured yourself cancellation of your WO's promotion of cell proliferation. Worse, admining MGF Post WO will not kiick start proliferation either, not in the presense of IGF it won't.

This is like when people tell me they'll admin a secretagogue combo, followed by IGF. What are we thinking when we do this? Are we really wanting to cancel out the secretion effect of the combo? Yes, IGF will also cancel out GH secretion as well. The thinking behind this is well umm, not thought out. You're wasting your combo and in the previous, you're wasting the MGF.

This all boils down to the other 3 questions I asked -
1. What invokes MGF?
2. What is MGF - what's its purpose?
3. What is IGF - what's its purpose?

If you know this, you'll have an idea on when to admin. However when someone tells me that they are experiencing results, I have no doubt they are. Admin GH, IGF, MGF whenever you want. But receiving what you believe to be the best results, doesn't necessarily mean you actually are.

Good luck.

 

[123cctv]

seems to be working...

Thanks for trying it and chiming in plang. I'd tell someone sleptical, ignore what I am saying, though this is based on data, try it for a couple of weeks and then chime in.

 

[stike]

Data is generally fact. Belief on the other hand? Well, we're not discussing belief here are we?

Most understand there are better times than others to administer a substance. Take GH for instance, I can show you optimal times of admin. Further, based on common sense questions I gave you above, it might occur there are better times to admin for optimal response/gains. For instance, take this question -

4. When are binding protiens which inhibit the peptides anabolic effects at their lowest?

Is the answer to this question, Pre WO? Course not. Thus if so, then why would any one admin it when its effects (anabolic ) will be blunted? I asked another question -

3. What if one peptide cancels out the other?

You're aware IGF cancels out MGF expression? It does. But here's the biggest catch of this mess - exactly when does MGF expression (proliferation) occur? When muscles are torn/damaged, i..e a WO. By admin'ing IGF pre WO you have actually assured yourself cancellation of your WO's promotion of cell proliferation. Worse, admining MGF Post WO will not kiick start proliferation either, not in the presense of IGF it won't.

This is like when people tell me they'll admin a secretagogue combo, followed by IGF. What are we thinking when we do this? Are we really wanting to cancel out the secretion effect of the combo? Yes, IGF will also cancel out GH secretion as well. The thinking behind this is well umm, not thought out. You're wasting your combo and in the previous, you're wasting the MGF.

This all boils down to the other 3 questions I asked -
1. What invokes MGF?
2. What is MGF - what's its purpose?
3. What is IGF - what's its purpose?

If you know this, you'll have an idea on when to admin. However when someone tells me that they are experiencing results, I have no doubt they are. Admin GH, IGF, MGF whenever you want. But receiving what you believe to be the best results, doesn't necessarily mean you actually are.

Good luck.

If IGF cancels gh secretion.How long after gh should Igf be admins.Are we talking a couple hours.

 

[plang]

Thanks for trying it and chiming in plang. I'd tell someone sleptical, ignore what I am saying, though this is based on data, try it for a couple of weeks and then chime in.

Are we sure igf-1 cancels out Injected mgf? Since there are no mgf receptors the mgf we inject really acts like igf...just a slightly different variant....because the mgf we really want to increase occurs within the cell itself.....

 

[Seabiscuit Hogg]

Are we sure igf-1 cancels out Injected mgf? Since there are no mgf receptors the mgf we inject really acts like igf...just a slightly different variant....because the mgf
we really want to increase occurs within the cell itself.....

Word. Endogenous mgf can be increased through pof type training. This also allows exo mgf to seep inside damaged muscle cells. I don't see how IGF-1 can negate this. Some exo mgf will work through IGF receptors and I'm not sure IGF-1 lr3 can hinder that much, due to it's lower affinity to IGF receptors.
Anecdotally, I know this works pretty good through exp. I will try it the other way with IGF DES tho.

 

[123cctv]

Are we sure igf-1 cancels out Injected mgf?

As sure as I can be, yes.

Since there are no mgf receptors the mgf we inject really acts like igf.

MGF generally expresses differentiation (IGF expression) IF the environment is such.

 

[The Dude]

Data is generally fact. Belief on the other hand? Well, we're not discussing belief here are we?

Most understand there are better times than others to administer a substance. Take GH for instance, I can show you optimal times of admin. Further, based on common sense questions I gave you above, it might occur there are better times to admin for optimal response/gains. For instance, take this question -

4. When are binding protiens which inhibit the peptides anabolic effects at their lowest?

Is the answer to this question, Pre WO? Course not. Thus if so, then why would any one admin it when its effects (anabolic ) will be blunted? I asked another question -

3. What if one peptide cancels out the other?

You're aware IGF cancels out MGF expression? It does. But here's the biggest catch of this mess - exactly when does MGF expression (proliferation) occur? When muscles are torn/damaged, i..e a WO. By admin'ing IGF pre WO you have actually assured yourself cancellation of your WO's promotion of cell proliferation. Worse, admining MGF Post WO will not kiick start proliferation either, not in the presense of IGF it won't.

This is like when people tell me they'll admin a secretagogue combo, followed by IGF. What are we thinking when we do this? Are we really wanting to cancel out the secretion effect of the combo? Yes, IGF will also cancel out GH secretion as well. The thinking behind this is well umm, not thought out. You're wasting your combo and in the previous, you're wasting the MGF.

This all boils down to the other 3 questions I asked -
1. What invokes MGF?
2. What is MGF - what's its purpose?
3. What is IGF - what's its purpose?

If you know this, you'll have an idea on when to admin. However when someone tells me that they are experiencing results, I have no doubt they are. Admin GH, IGF, MGF whenever you want. But receiving what you believe to be the best results, doesn't necessarily mean you actually are.

Good luck.

Its clear you have extensive knowledge in this area. Mine is more academic and anecdotal. My B.S. from FSU is in Biomedical Science, but as you know topics like this are rarely even mentioned much less studied in depth. That being said I am interesting in what dosing protocol you would suggest for IGF / MGF, CJC / GHRP. Back to back comparisons obviously aren't going to happen as I'm not going to give back the new growth and tissue as well as the 11lbs my current protocol has produced, but I am EXTREMELY interested in various dosing protocol and the science behind them. The problem is that the tried and true science as it pertains to us isn't there. Its up to us to blaze the path. Normal pathways that are studied and published simply don't apply to us as our bodies are in an entirely different metabolic state and our training is far more damaging that anythign that has been studies.
Spread the wealth Brotha!

 

[plang]

As sure as I can be, yes.



MGF generally expresses differentiation (IGF expression) IF the environment is such.

Must be a long day.....dat thinks native mgf acts like fgf.....it iduces proliferation and inhibits differentiation http://www.professionalmuscle.com/f...c-1295-ghrp-6-basic-guides-38.html#post532884

he also states in that post how he thinks peg mgf, mgf (exogenous forms of mgf) really act like igf.....which can either proliferate or differentiate.....meaning that using it pwo would be the wrong time.....but again all this is based on conjecture as dat is trying to draw conclusions based off of fgf.....meaning in the end we are just guessing to a degree.....and IMO anecdotal results based on some science is the beat authority.....because if you read that post it further solidifies that nonone knows exactly how tonsoae these peptides...even the super brain dat....

 

[123cctv]

Must be a long day.....dat thinks native mgf acts like fgf.....it iduces proliferation and inhibits differentiation http://www.professionalmuscle.com/f...c-1295-ghrp-6-basic-guides-38.html#post532884

I think you're missing the overall. Dat is still saying the same thing I am saying, even in this post you brought up. It's funny, I can't believe this has been going on more than a week now. I started out by pointing out how Ron is backwards in his thinking. Course what's crazy though with Ron, there was no science offered with his statements, yet it was accepted without question. Now we're onto DatBtrue. God help me if this mans whistling a different tune than I. Let's examine his statements out of this post you brought out.


1. "To stop proliferation you induce differentiation. To promote proliferation you arrest differentiation."

I've been spouting this over and over again. Heh, thankfully Dat said it, now we can all be assured it's law. We'll get to what can change synthesis in Dat's post in a sec. Next he said,...

2. "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."

Back to the fact of wanting proliferation to have time to work, otherwise you're just wasting your MGF! Again, MGF expression = proliferation. By the way, it was already pointed out in another thread re: MGF can also differentiate. I've never once even insinuated otherwise. Maybe this is being missed? If so, then God help me from now on as it appears I'm doomed to explaining every minor detail in my posts. The amount of data I generally type already, is usually exhausting enough as is. Further, rest assured when I am in disagreement with a matter, I always make it known.

In all actuality, and this is where this post is going = MGF has an identity crisis, just like many other folks seem to have. They get around particular types of people and they begin to act differently, even acting similar. That is MGF! If IGF is hangin around, MGF will begin to differentiate just like IGF. However if the IGF is no where to be found, MGF is capable of proliferating.

To continue. Dat references a study utlizing TGF, FGF and IGF. Howver what is relevant to what I have been saying? Note the following:

3. IGF-I stimulated proliferation to a small degree but demonstrated a more pronounced stimulation of differentiation. AND "...differentiation with minimal proliferation resulted from treatment with IGF-I, alone."

In other words, IGF by itself and in the above study (there are other studies) IGF is partially capable of proliferation, BUT in general, invokes differentiation! Of course it has also been shown MGF can do either (proliferation or differentiation) solely dependant upon environment! MGF, Mr. Identity Crisis himself.

Next, what did our man DatBtrue state? He said,

4. "TGF-beta is present naturally at the time of injury," , or let's accept this as conditions met in a WO, i.e. damaged muscles, he goes on, "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."

Now without going on and on, note Dat's conclusions:

5. "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."

He further said,

6. "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."

This to me is becoming a broken record. I've been saying over and over again you do not want to admin IGF post WO, not without waiting a while. The other day (in another thread) Dat's statements were being examined as well. I searched his thoughts on MGF at that time, wanting to verify we're not contradicting each other. Here are some quotations relevant to these concerns.

From da Dat desk,

"If you can make IGF-1 proliferate then okay but normally if differentiates. When you introduce a differentiator suddenly all of the proliferation stops and the differentiator goes about turning satellite cells into end product cells (myotubes)."

"See your native MGF expression works post workout. You don't interfere with it by inducing differentiation w/ external admin of IGF-1 until later,"

"exogenously administered IGF1 will interfere with MGF expression".

"The focus needs to be on proliferation versus differentiation. Insulin-like growth factor-I can induce proliferation in some environments in the presence of some compounds. In other environments and in the absence of those compounds it promotes differentiation."

"most studies indicate that testosterone is an inhibitory factor of cell proliferation"

Now these quotations were not taken out of any reasonable context that hasn't already been addressed. No, I didn't retain what posts I retrieved them from. However I wouldn't play that game with anyone in here. They are as they appear. Though if concerned, please search them out and we'll once again, line by line, address his statements.

Bottom line - exo IGF-1 promotes differentiation. Further, it will "interfere" or as I said, "cancels out" or blunts MGF expression. The only exception to this rule and according to this study is that TGF-beta must exist (at the damaged site) for MGF to continue proliferating in the presence of IGF-1. Anywhere else and under any other condition, IGF becomes the mediator of MGF's identity.

 

[123cctv]

That being said I am interesting in what dosing protocol you would suggest for IGF / MGF, CJC / GHRP.

How would I use the above? If pushing extremes,

Combo 3-4x per day
Combo Pre WO.
MGF Pre or Post WO
IGF-1 would vary. I'd mix this up anywhere between 2-10 hours Post WO.

 

[bulldog spirit]

Were would you guys use gh if using insulin pre wo and mgf post wo then igf 1/2 hour later. (10ius gh for mass) cheers.

 

[plang]

but dat also states that exogenous admin mgf or peg mgf acts like igf in the body...so we would want to avoid mgf pwo....

From dat:

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.


And why does inducing differentiation pre workout atop pwo proliferation? I haven't seen anything saying it does... Is it not the workout itself that induces proliferation?

I question not to prove wrong...but or knowledge...because just like the dude my flawed protocol has worked in spades so far...I'm always looming to improve an or change

 

[juicin]

I think you're missing the overall. Dat is still saying the same thing I am saying, even in this post you brought up. It's funny, I can't believe this has been going on more than a week now. I started out by pointing out how Ron is backwards in his thinking. Course what's crazy though with Ron, there was no science offered with his statements, yet it was accepted without question. Now we're onto DatBtrue. God help me if this mans whistling a different tune than I. Let's examine his statements out of this post you brought out.


1. "To stop proliferation you induce differentiation. To promote proliferation you arrest differentiation."

I've been spouting this over and over again. Heh, thankfully Dat said it, now we can all be assured it's law. We'll get to what can change synthesis in Dat's post in a sec. Next he said,...

2. "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."

Back to the fact of wanting proliferation to have time to work, otherwise you're just wasting your MGF! Again, MGF expression = proliferation. By the way, it was already pointed out in another thread re: MGF can also differentiate. I've never once even insinuated otherwise. Maybe this is being missed? If so, then God help me from now on as it appears I'm doomed to explaining every minor detail in my posts. The amount of data I generally type already, is usually exhausting enough as is. Further, rest assured when I am in disagreement with a matter, I always make it known.

In all actuality, and this is where this post is going = MGF has an identity crisis, just like many other folks seem to have. They get around particular types of people and they begin to act differently, even acting similar. That is MGF! If IGF is hangin around, MGF will begin to differentiate just like IGF. However if the IGF is no where to be found, MGF is capable of proliferating.

To continue. Dat references a study utlizing TGF, FGF and IGF. Howver what is relevant to what I have been saying? Note the following:

3. IGF-I stimulated proliferation to a small degree but demonstrated a more pronounced stimulation of differentiation. AND "...differentiation with minimal proliferation resulted from treatment with IGF-I, alone."

In other words, IGF by itself and in the above study (there are other studies) IGF is partially capable of proliferation, BUT in general, invokes differentiation! Of course it has also been shown MGF can do either (proliferation or differentiation) solely dependant upon environment! MGF, Mr. Identity Crisis himself.

Next, what did our man DatBtrue state? He said,

4. "TGF-beta is present naturally at the time of injury," , or let's accept this as conditions met in a WO, i.e. damaged muscles, he goes on, "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."

Now without going on and on, note Dat's conclusions:

5. "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."

He further said,

6. "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."

This to me is becoming a broken record. I've been saying over and over again you do not want to admin IGF post WO, not without waiting a while. The other day (in another thread) Dat's statements were being examined as well. I searched his thoughts on MGF at that time, wanting to verify we're not contradicting each other. Here are some quotations relevant to these concerns.

From da Dat desk,

"If you can make IGF-1 proliferate then okay but normally if differentiates. When you introduce a differentiator suddenly all of the proliferation stops and the differentiator goes about turning satellite cells into end product cells (myotubes)."

"See your native MGF expression works post workout. You don't interfere with it by inducing differentiation w/ external admin of IGF-1 until later,"

"exogenously administered IGF1 will interfere with MGF expression".

"The focus needs to be on proliferation versus differentiation. Insulin-like growth factor-I can induce proliferation in some environments in the presence of some compounds. In other environments and in the absence of those compounds it promotes differentiation."

"most studies indicate that testosterone is an inhibitory factor of cell proliferation"

Now these quotations were not taken out of any reasonable context that hasn't already been addressed. No, I didn't retain what posts I retrieved them from. However I wouldn't play that game with anyone in here. They are as they appear. Though if concerned, please search them out and we'll once again, line by line, address his statements.

Bottom line - exo IGF-1 promotes differentiation. Further, it will "interfere" or as I said, "cancels out" or blunts MGF expression. The only exception to this rule and according to this study is that TGF-beta must exist (at the damaged site) for MGF to continue proliferating in the presence of IGF-1. Anywhere else and under any other condition, IGF becomes the mediator of MGF's identity.

I think its time we get you a sticky like Dat has

The amount of knowledge you bring to this forum is immeasurable.

 

[123cctv]

but dat also states that exogenous admin mgf or peg mgf acts like igf in the body...so we would want to avoid mgf pwo....

Sorry bro, but no, Dat hasn't said that in any post I have ever read. What he has said is that MGF "CAN" assume the role of IGF (differentiation), but is determinant by the environment itself and or the presence of particular compounds. It is this and this only, that I'm claiming and I have seen Dat claim. Now if Dat has ever said anything contrary to this, please show me where and let's address that, because I'm convinced there is a misunderstanding.

From dat:

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 believe you have misinterpreted what Dat is said. On the surface, this statement taken in its literal form is an oxymoron! Hopefully that's not what Dat meant. Cause if so, he just said,

"you do not want to take IGF (or MGF) post WO where your body creates & utilizes MGF...that is post-weightlifting"

Is this what you're suggesting Dat said here?? If so, DaBtrue is seriuosly confused and I don't buy into that. What am I suggetsing he said was,...

"you do not want to take IGF (or IGF attempting to act like MGF) post WO where your body creates & utilizes MGF...that is post-weightlifting"

And why does inducing differentiation pre workout atop pwo proliferation? I haven't seen anything saying it does.

plang, I don't know what you mean. Did you overlook the earlier statements? If not, how do you interpret this?

"See your native MGF expression works post workout. You don't interfere with it by inducing differentiation w/ external admin of IGF-1 until later,"

"exogenously administered IGF1 will interfere with MGF expression".

No offense, as I respect your input. However how do you interpret these comments by da Dat? Don't they clearly say, do not inject IGF or you will interfere with MGF expression?

Is it not the workout itself that induces proliferation?

Yes it is! And that's been the key here all along. Iintroduction of a differentiator (IGF), environment dependant is capable of overriding MGF expression.

Even the study you elected to produce refected that (as Dat said,) "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."

Of course, this is all in hopes that FGF acts exactly like MGF, though no one in here is taking FGF to my knowledge.

I hope this helps. If not, then I'm doomed to go deeper. Course, that worries me now, considering what has been presented thus far?

 

[123cctv]

I think its time we get you a sticky like Dat has .

Thanks Juicin!

But please don't give me a sticky or it'll be the death of me!

 

[plang]

Quote:
Originally Posted by pitbulladams
your opinion/view on PegMGF use ?
To quickly summarize the difference in function, MGF stimulates muscle stem cells (satellite cells) to reenter the cell cycle and proliferate, whereas IGF-1 is necessary for the differentiation of newly generated muscle precursor cells into myoblasts and myofibers. See material from Goldspink posted earlier in this thread at: Post #158 Mechanical Signals, IGF-I Gene Splicing, and Muscle Adaptation


Growth Hormone bound to its receptor in the liver activates the STAT5b signaling pathway which promotes movement of that activated signaling protein to the nucleus where it induces transcription of the IGF-1 gene. From studies in mice and humans, it is evident that GH induces expression of both the endocrine form of IGF-1, the muscle form of IGF-1 and MGF. 1 Mice deficient in GH (lit/lit mice) respond to administration of GH with an acute increase in MGF, but not IGF-1, in skeletal muscle, although IGF-1 in liver is increased. 2 However the precise mechanism by which GH has distinct effects on IGF-1 and MGF expression in muscle is not completely known.

What is known is that in response to stretch overload and the presence of growth hormone combined gene transcription in muscle and its subsequent "blueprint" assembly" are induced to create mechano growth factor (MGF also known as IGF-1Ec in humans or IGF-1EB in mice) instead of muscle IGF-1. 3

How does the behavior of IGF-1 and MGF differ?

"MGF is a non-secreted form of IGF-1 that can be found in the nucleus of cells in culture or in a perinuclear location in hippocampal cells after ischemia (restriction in blood supply)". 4

In other words MGF never leaves the cell it was created in. For emphasis I quote from another source:

"...MGF... is not normally secreted." 5

Geoffrey Goldspink has written "that MGF increases myoblast proliferation via a different signalling pathway" then IGF-1.

To reiterate & expand upon this concept I quote from another source:

"IGF-1 isoforms differ in the signaling pathways they activate. By over-expressing IGF-1Ea and MGF in muscle, it has been shown that both isoforms can activate IGF-1R and AKT phosphorylation. In addition, MGF was shown to induce phosphorylation of ERK, a property not shared with IGF-1Ea." 6

So IGF-1 and MGF work through different pathways not receptors. There is only one receptor, IGF-1-receptor (also insulin, IGF-II & hybrid receptors which are not relevant to this discussion). There is no MGF receptor. The reason why it would be nonsensical to have an MGF receptor is that MGF does not leave the cell.

This contrasts with IGF-1 which is released from the liver into circulation and which is created in muscle and translocates to the cell surface. Both events result in IGF-1 binding to the IGF-1 receptor.

So what happens in plain language please?

During the process of gene transcription pieces of DNA are transcribed and then spliced together by RNA and this code is taken to the ribosomes where the peptide is manufactured. In splicing MGF there is a subtle frame shift such that the right side of the code is a little different then IGF-1. Everything else is identical.

This subtle difference means that when MGF & IGF-1 are manufactured by the riboomes MGF MUST because of the signal pull that is part of its make up, translocate to the Nucleus of the cell and more specifically the Nucleolus.

IGF-1 because of its makeup MUST move to the cytoplasm where it forms a pool of IGF-1 which will transloacte to the cell membrane where it will bind w/ an IGF-1 receptor.

MGF has NO receptor. It does not need it to mediate events. Too many times people think that a lock/key ligand/receptor is needed to intiate signals. That is not always true especially when proteins move to the nucleus.

MGF is NEVER found in circulation. It is produced in a muscle cell as described and it will act there always.

IGF-1 however does circulate. It is produced in the liver and secreted into the blood stream. If it is made in muscle tissue or in local tissue it makes its way to the surface and can bind to a receptor on that cell or nearby cells. The latter is how muscle made IGF-1 can effect nearby bone growth.

In lab experiments with MGF they usually do one of two things. One they use a viral vector of MGF cDNA to increase the cDNA of MGF in the cell so that more MGF is made internally. When they do this they get a 25% increase in muscle in a three week period. If they use the same approach to get IGF-1 to express itself from within they get less muscle growth (15%) and it takes 4 months.

The second approach is to actually inject MGF into a cell (i.e. penetrate the cell membrane). Unfortunately for scientists this also invokes a damage repair function in cells so it is difficult to actually attribute all of the benefits that ensue to MGF.

You follow neither of these approaches when you inject MGF or Peg MGF.

MGF is identical to IGF-1 in chemical makeup on the leftside of the peptide. This allows it to bind with IGF-1 receptors should it ever be injected or find itself outside of the cell. However because of the difference in right-side structure MGF is incapable of binding to IGF-1 binding proteins (which would prolong its life).

MGF has a very short half-life in blood plasma. If it is pegylated it has a longer half-life. I do not know the extent to which pegylation reduces binding affinity but it probably does to some extent depending on where it is pegylated.

Injecting Peg MGF will, if it survives, probably bind to an IGF-1 receptor. If it does so it activates the IGF-1 signaling pathways just as IGF-1 would.

I do not have any data on how strongly MGF will bind to IGF-1 receptors. A pegylated MGF is small enough to penetrate the vascular wall and travel systemically. It will not be confined to the area injected as IGF-1 bound to IGF-BindingProtein3 bound to Acid laibile subunit (i.e. the ternary complex) will. Thats why injecting large amounts of MGF brings vacularization, pumps, glucose uptake, in essence insulin-like activity....because it is behaving as IGF-1...and doing so in systemic fashion.

Some science (derived from ref:5) followed by both a reiteration and an elaboration on my part.

The IGF-1 gene consists of 6 exons (DNA bases that are transcribed into mRNA and eventually code for amino acids in the proteins), separated by 5 introns (DNA bases, which are found between exons, but are not transcribed). Transcription is controlled by alternate use of two upstream promoters and starts at several transcription start sites located in exons 1 and 2. Together, alternate promoter usage and alternative splicing at the 5' and 3' ends of the gene generate several distinct mRNAs depending on their exon sequences, which code for three isoforms of precursor IGF-1.

Note: The notation 5' and 3' refer to the direction of the DNA template in the chromosome and is used to distinguish between the two untranslated regions (grey). See the example below:



These isoforms have characteristic N-terminal signal peptide sequences and C-terminal extension (E) peptide domains. Exons 1 and 2 and part of exon 3 encode the signal peptides. The remainder of exon 3 and exon 4 encode the mature IGF-1 peptide and the proximal part of the E peptide, which are shared by all isoforms. Splicing of exon 4 to exon 6 generates the predominant transcript IGF-1Ea. Splicing of exon 4 to exon 5 generates IGF- 1Eb, which encodes an isoform with 47 distinct amino acids in the E domain. When part of exon 5 is spliced to exon 6, the IGF- 1Ec (IGF-1EB in mouse) variant is generated. In this case, a frame-shift occurs in exon 5 followed by premature transcription stop in exon 6 that results in a stretch of 25 amino acids unique to this variant.



As a result these templates produce in cellular ribosomes IGF-1 peptide forms that differ in amino acid structure in the E peptide region. This results in different C-terminal regions for the IGF-1 & MGF peptides. MGF BECAUSE of its C-terminal sequence, upon "birth" becomes rapidly localized in the nucleus. It is the carboxy portion which draws either MGF or the altered portion to the nucleus rather than to the cell membrane.
"We found that the isoform of the human IGF-I precursor encoded by exon 5 [MGF] localized to the nucleus and strongly to the nucleolus. Precursors containing exon 6 or the upstream portion of exon 5 did not...The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain." 4
MGF is an autocrine growth factor, and this is THE different signaling pathway...a pathway that does not involve any receptor. The action of MGF via this pathway is one of promoting myoblast proliferation.

However MGF maintains a dual action. It "activates the muscle stem cell pool through its C-terminal domain (encoded in exons 5 and 6) as mentioned above AND according to the various studies by Geoffrey Goldspink "increases anabolic effects as the result of its IGF-I receptor binding domain (encoded in exons 3 and 4), which all the IGF-I genes possess."

The unaltered portion of MGF is still capable of binding to the IGF-Receptor. The altered carboxy portion renders MGF incapable of binding to the IGF-1-Binding proteins BUT it possesses the ability to bind to the IGF-1-Receptor via the unaltered side.

So what if MGF is injected into plasma? Presumably it would bind to the IGF-1-Receptor and initiate the AKT signaling pathway which will stimulate cell growth signals. In other words MGF stops being MGF and behaves like IGF-1 in initiating anabolic events. But it has been shown but is not yet fully understood that MGF is capable of AKT phosphorylation (an IGF-1-IGF-1-receptor mediated event) without ever coming in contact with the IGF-1-receptor.

This brings up an interesting point. MGF seems to be capable of performing both its unique duties and those of IGF-1 as well (at times).

What about studies that inject MGF into subjects?

Actually they don't do it that way.

"One of the methods we used to establish the biological action of MGF was to engineer a gene into which its cDNA was inserted into a vector. To our surprise a single intramuscular injection into a mouse muscle resulted in a 25% increase in mean muscle fibre cross section area within three weeks." - Goldspink G, Yang SY. Method of treating muscular disorders, United States Patent. Patent No US 6,221,842 B1, Apr 24, 2001.

This contrasts with, "similar experiments carried out using the systemic or liver type of IGF-I in an adenoviral vector under the control of a muscle regulatory sequence. This took four months to produce a 15% increase and is probably due to the anabolic effect of IGF-I, which is common to all the splice variants." - Barton-Davis E, Shoturma DI, Musaro A, et al. Viral mediated expression of insulin-like growth factor-I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 1998;95:15603–7.

So obviously the endogenous expression of MGF is much more powerful then the endogenous expression of IGF-1. Therefore we want MGF to behave as MGF and not as IGF-1 and do so in autocrine fashion.

In fact in an anti-doping article Goldspink made the following observation "The use of the DNA of IGF-I and particularly MGF is therefore a prime candidate for gene doping for enhancement of athletic performance."

Compare this to how bodybuilders have been attempting to use MGF. They simply inject the peptide. So even if it is resistant to breakdown (via PEGylation) and it binds locally to the IGF-1 receptor there will be NO MGF primary action. Instead MGF will behave as an IGF-1 ligand, binding to the IGF-1-Receptor to mediate IGF-1 signaling events.
References:

1 - Hameed, M., Lange, K.H., Andersen, J.L., Schjerling, P., Kjaer, M., Harridge, S.D., Goldspink, G., 2004. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J. Physiol. 555, 231–240.

2 - Iida, K., Itoh, E., Kim, D.S., del Rincon, J.P., Coschigano, K.T., Kopchick, J.J., Thorner, M.O., 2004. Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice. J. Physiol. 560, 341–349.

3 - McKoy, Godfrina et al.,Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation, Journal of Physiology (1999), 516.2, pp. 583—592 583

4 - Tan DS, Cook A, and Chew SL. Nucleolar localization of an isoform of the IGF-I precursor. BMC Cell Biol 3: 17, 2002.

5 - Scrable, Heidi, Running on empty: How p53 controls INS/IGF signaling and affects life span, Experimental Gerontology xxx (2008) xxx–xxx

6 - Barton, E.R., 2006. Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle. J. Appl. Physiol. 100, 1778– 1784.

 

[plang]

I know he doesn't like this but...here is a post from his private forum where he states again that he/we really don't know what mgf does pwo

Well if MGF behaves as IGF-1 it will be acting to differentiate "cells" not proliferating them. The weight-lifting event itself should result in an increase in native MGF which is an autocrine growth factor only and this is proliferative.

It appears that in the presence of IGF-1 proliferation stops and those new "cells" are tasked... which means they will no longer proliferate.

So the worst time to inject IGF-1 (or MGF IF IF IF it is acting as IGF-1) is PWO. So I would expect that if someone uses these things PWO they are actually hindering what would have occurred naturally.
Proliferate [Native MGF]->Proliferate [Native MGF]->Proliferate [Native MGF]->Proliferate [Native MGF]->Proliferate [Native MGF]->Differentiate[Native IGF-1 OR exogenous IGF-1/MGF]
is better then:
Proliferate->Differentiate [IGF-1 exogenous]

 

[cm]

this is some good info going back and forth. Both sides seem like good arguments, but I have a question in regards to timing your carbohydrates. If taken pre workout, it usually is accompanied by sugar, caffiene, creatine, arginine, etc, whatever you like, but sugar for sure.
Now what about the thinking of taking the igf @ 2 or more hours after the exercise?
carb ingestion surrounding like preworkout? Something different?
thanks fellas
-c

 

[123cctv]

Quote:
Originally Posted by pitbulladams
your opinion/view on PegMGF use ?
To quickly summarize the difference in function, MGF stimulates muscle stem cells (satellite cells) to reenter the cell cycle and proliferate, whereas IGF-1 is necessary for the differentiation of newly generated muscle precursor cells into myoblasts and myofibers. See material from Goldspink posted earlier in this thread at: Post #158 Mechanical Signals, IGF-I Gene Splicing, and Muscle Adaptation


Growth Hormone bound to its receptor in the liver activates the STAT5b signaling pathway which promotes movement of that activated signaling protein to the nucleus where it induces transcription of the IGF-1 gene. From studies in mice and humans, it is evident that GH induces expression of both the endocrine form of IGF-1, the muscle form of IGF-1 and MGF. 1 Mice deficient in GH (lit/lit mice) respond to administration of GH with an acute increase in MGF, but not IGF-1, in skeletal muscle, although IGF-1 in liver is increased. 2 However the precise mechanism by which GH has distinct effects on IGF-1 and MGF expression in muscle is not completely known.

What is known is that in response to stretch overload and the presence of growth hormone combined gene transcription in muscle and its subsequent "blueprint" assembly" are induced to create mechano growth factor (MGF also known as IGF-1Ec in humans or IGF-1EB in mice) instead of muscle IGF-1. 3

How does the behavior of IGF-1 and MGF differ?

"MGF is a non-secreted form of IGF-1 that can be found in the nucleus of cells in culture or in a perinuclear location in hippocampal cells after ischemia (restriction in blood supply)". 4

In other words MGF never leaves the cell it was created in. For emphasis I quote from another source:

"...MGF... is not normally secreted." 5

Geoffrey Goldspink has written "that MGF increases myoblast proliferation via a different signalling pathway" then IGF-1.

To reiterate & expand upon this concept I quote from another source:

"IGF-1 isoforms differ in the signaling pathways they activate. By over-expressing IGF-1Ea and MGF in muscle, it has been shown that both isoforms can activate IGF-1R and AKT phosphorylation. In addition, MGF was shown to induce phosphorylation of ERK, a property not shared with IGF-1Ea." 6

So IGF-1 and MGF work through different pathways not receptors. There is only one receptor, IGF-1-receptor (also insulin, IGF-II & hybrid receptors which are not relevant to this discussion). There is no MGF receptor. The reason why it would be nonsensical to have an MGF receptor is that MGF does not leave the cell.

This contrasts with IGF-1 which is released from the liver into circulation and which is created in muscle and translocates to the cell surface. Both events result in IGF-1 binding to the IGF-1 receptor.

So what happens in plain language please?

During the process of gene transcription pieces of DNA are transcribed and then spliced together by RNA and this code is taken to the ribosomes where the peptide is manufactured. In splicing MGF there is a subtle frame shift such that the right side of the code is a little different then IGF-1. Everything else is identical.

This subtle difference means that when MGF & IGF-1 are manufactured by the riboomes MGF MUST because of the signal pull that is part of its make up, translocate to the Nucleus of the cell and more specifically the Nucleolus.

IGF-1 because of its makeup MUST move to the cytoplasm where it forms a pool of IGF-1 which will transloacte to the cell membrane where it will bind w/ an IGF-1 receptor.

MGF has NO receptor. It does not need it to mediate events. Too many times people think that a lock/key ligand/receptor is needed to intiate signals. That is not always true especially when proteins move to the nucleus.

MGF is NEVER found in circulation. It is produced in a muscle cell as described and it will act there always.

IGF-1 however does circulate. It is produced in the liver and secreted into the blood stream. If it is made in muscle tissue or in local tissue it makes its way to the surface and can bind to a receptor on that cell or nearby cells. The latter is how muscle made IGF-1 can effect nearby bone growth.

In lab experiments with MGF they usually do one of two things. One they use a viral vector of MGF cDNA to increase the cDNA of MGF in the cell so that more MGF is made internally. When they do this they get a 25% increase in muscle in a three week period. If they use the same approach to get IGF-1 to express itself from within they get less muscle growth (15%) and it takes 4 months.

The second approach is to actually inject MGF into a cell (i.e. penetrate the cell membrane). Unfortunately for scientists this also invokes a damage repair function in cells so it is difficult to actually attribute all of the benefits that ensue to MGF.

You follow neither of these approaches when you inject MGF or Peg MGF.

MGF is identical to IGF-1 in chemical makeup on the leftside of the peptide. This allows it to bind with IGF-1 receptors should it ever be injected or find itself outside of the cell. However because of the difference in right-side structure MGF is incapable of binding to IGF-1 binding proteins (which would prolong its life).

MGF has a very short half-life in blood plasma. If it is pegylated it has a longer half-life. I do not know the extent to which pegylation reduces binding affinity but it probably does to some extent depending on where it is pegylated.

Injecting Peg MGF will, if it survives, probably bind to an IGF-1 receptor. If it does so it activates the IGF-1 signaling pathways just as IGF-1 would.

I do not have any data on how strongly MGF will bind to IGF-1 receptors. A pegylated MGF is small enough to penetrate the vascular wall and travel systemically. It will not be confined to the area injected as IGF-1 bound to IGF-BindingProtein3 bound to Acid laibile subunit (i.e. the ternary complex) will. Thats why injecting large amounts of MGF brings vacularization, pumps, glucose uptake, in essence insulin-like activity....because it is behaving as IGF-1...and doing so in systemic fashion.

Some science (derived from ref:5) followed by both a reiteration and an elaboration on my part.

The IGF-1 gene consists of 6 exons (DNA bases that are transcribed into mRNA and eventually code for amino acids in the proteins), separated by 5 introns (DNA bases, which are found between exons, but are not transcribed). Transcription is controlled by alternate use of two upstream promoters and starts at several transcription start sites located in exons 1 and 2. Together, alternate promoter usage and alternative splicing at the 5' and 3' ends of the gene generate several distinct mRNAs depending on their exon sequences, which code for three isoforms of precursor IGF-1.

Note: The notation 5' and 3' refer to the direction of the DNA template in the chromosome and is used to distinguish between the two untranslated regions (grey). See the example below:



These isoforms have characteristic N-terminal signal peptide sequences and C-terminal extension (E) peptide domains. Exons 1 and 2 and part of exon 3 encode the signal peptides. The remainder of exon 3 and exon 4 encode the mature IGF-1 peptide and the proximal part of the E peptide, which are shared by all isoforms. Splicing of exon 4 to exon 6 generates the predominant transcript IGF-1Ea. Splicing of exon 4 to exon 5 generates IGF- 1Eb, which encodes an isoform with 47 distinct amino acids in the E domain. When part of exon 5 is spliced to exon 6, the IGF- 1Ec (IGF-1EB in mouse) variant is generated. In this case, a frame-shift occurs in exon 5 followed by premature transcription stop in exon 6 that results in a stretch of 25 amino acids unique to this variant.



As a result these templates produce in cellular ribosomes IGF-1 peptide forms that differ in amino acid structure in the E peptide region. This results in different C-terminal regions for the IGF-1 & MGF peptides. MGF BECAUSE of its C-terminal sequence, upon "birth" becomes rapidly localized in the nucleus. It is the carboxy portion which draws either MGF or the altered portion to the nucleus rather than to the cell membrane.
"We found that the isoform of the human IGF-I precursor encoded by exon 5 [MGF] localized to the nucleus and strongly to the nucleolus. Precursors containing exon 6 or the upstream portion of exon 5 did not...The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain." 4
MGF is an autocrine growth factor, and this is THE different signaling pathway...a pathway that does not involve any receptor. The action of MGF via this pathway is one of promoting myoblast proliferation.

However MGF maintains a dual action. It "activates the muscle stem cell pool through its C-terminal domain (encoded in exons 5 and 6) as mentioned above AND according to the various studies by Geoffrey Goldspink "increases anabolic effects as the result of its IGF-I receptor binding domain (encoded in exons 3 and 4), which all the IGF-I genes possess."

The unaltered portion of MGF is still capable of binding to the IGF-Receptor. The altered carboxy portion renders MGF incapable of binding to the IGF-1-Binding proteins BUT it possesses the ability to bind to the IGF-1-Receptor via the unaltered side.

So what if MGF is injected into plasma? Presumably it would bind to the IGF-1-Receptor and initiate the AKT signaling pathway which will stimulate cell growth signals. In other words MGF stops being MGF and behaves like IGF-1 in initiating anabolic events. But it has been shown but is not yet fully understood that MGF is capable of AKT phosphorylation (an IGF-1-IGF-1-receptor mediated event) without ever coming in contact with the IGF-1-receptor.

This brings up an interesting point. MGF seems to be capable of performing both its unique duties and those of IGF-1 as well (at times).

What about studies that inject MGF into subjects?

Actually they don't do it that way.

"One of the methods we used to establish the biological action of MGF was to engineer a gene into which its cDNA was inserted into a vector. To our surprise a single intramuscular injection into a mouse muscle resulted in a 25% increase in mean muscle fibre cross section area within three weeks." - Goldspink G, Yang SY. Method of treating muscular disorders, United States Patent. Patent No US 6,221,842 B1, Apr 24, 2001.

This contrasts with, "similar experiments carried out using the systemic or liver type of IGF-I in an adenoviral vector under the control of a muscle regulatory sequence. This took four months to produce a 15% increase and is probably due to the anabolic effect of IGF-I, which is common to all the splice variants." - Barton-Davis E, Shoturma DI, Musaro A, et al. Viral mediated expression of insulin-like growth factor-I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 1998;95:15603–7.

So obviously the endogenous expression of MGF is much more powerful then the endogenous expression of IGF-1. Therefore we want MGF to behave as MGF and not as IGF-1 and do so in autocrine fashion.

In fact in an anti-doping article Goldspink made the following observation "The use of the DNA of IGF-I and particularly MGF is therefore a prime candidate for gene doping for enhancement of athletic performance."

Compare this to how bodybuilders have been attempting to use MGF. They simply inject the peptide. So even if it is resistant to breakdown (via PEGylation) and it binds locally to the IGF-1 receptor there will be NO MGF primary action. Instead MGF will behave as an IGF-1 ligand, binding to the IGF-1-Receptor to mediate IGF-1 signaling events.
References:

1 - Hameed, M., Lange, K.H., Andersen, J.L., Schjerling, P., Kjaer, M., Harridge, S.D., Goldspink, G., 2004. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J. Physiol. 555, 231–240.

2 - Iida, K., Itoh, E., Kim, D.S., del Rincon, J.P., Coschigano, K.T., Kopchick, J.J., Thorner, M.O., 2004. Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice. J. Physiol. 560, 341–349.

3 - McKoy, Godfrina et al.,Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation, Journal of Physiology (1999), 516.2, pp. 583—592 583

4 - Tan DS, Cook A, and Chew SL. Nucleolar localization of an isoform of the IGF-I precursor. BMC Cell Biol 3: 17, 2002.

5 - Scrable, Heidi, Running on empty: How p53 controls INS/IGF signaling and affects life span, Experimental Gerontology xxx (2008) xxx–xxx

6 - Barton, E.R., 2006. Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle. J. Appl. Physiol. 100, 1778– 1784.

plang, was there an argument to be made in the above post? It contradicts nothing that I have said thus far. If you are simply pointing out that MGF can act like IGF, haven't I said this repeatedly? I have however added there are variants which will dictate how it responds. In the above post, he doesn't address this, though he has in others of which we have talked about already.

Of course, note Dat said,

"Therefore we want MGF to behave as MGF and not as IGF-1 and do so in autocrine fashion."

Agreed.

 

[123cctv]

Well if MGF behaves as IGF-1 it will be acting to differentiate "cells" not proliferating them.
It appears that in the presence of IGF-1 proliferation stops and those new "cells" are tasked... which means they will no longer proliferate.

Isn't the above what I've been saying all along?? Again, you are losing me.

So the worst time to inject IGF-1 (or MGF IF IF IF it is acting as IGF-1) is PWO.

plang, this could not be what he said, nor meant. If this is what he said, then it is an owymoron. May we examine his words please?

His quotation,

"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."

What you are suggesting he is saying is - we do not want to administer IGF OR MGF "in the environment where your body creates & utilizes MGF...that is post-weightlifting." That makes no sense! We do not want to admin MGF when our body is ultilizing MGF?? Huh??

That's like saying we do not want to admin a secretagogue combo at bedtime when our natural output of GH is secreted! That's ridiculous.

What Dat did say is we do not want to admin IGF (i.e. IGF running around pretending to be PEG MGF) "in the environment where your body creates & utilizes MGF...that is post-weightlifting." Please read his quotation again. Does this make sense now? To admin MGF when natural ouput exists would be about the only way we could have any say in assisting with its proposed expression.

In the next sentence after it (the very next line) he wrote, which should confirm the previous interpretation I gave,...

"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."

Sorry plang, just trying to help out here. A healthy debate, with no bickering intended.