IGF-1 and IGF-2 Peptides Hormones

Insulin-like growth factors 1 and 2 (IGF-1, IGF-2) are peptides that are similar in amino acid sequence and structure to insulin and can bind to the insulin receptor having the same glucose lowering effect1. IGF-1 and 2 also binds to the type 1 IGF receptor and are largely responsible for the growth promoting effects of growth hormone. The Type 1 IGF receptor also binds insulin but with lower affinity and is likely responsible for the anabolic effects of insulin beyond those of glucose uptake. There is a type 2 receptor but it only binds IGF-2 and does not appear to be involved with the anabolic effects of IGF-2. IGF-2 has largely been ignored as a promoter of skeletal muscle anabolism but since it signals through the same receptor as IGF-1, it will produce similar anabolic responses.

IGF-1 binds to the type-1 receptor which acts through a cascade of transcription and differentiation factors such as AKT, glycogen synthase kinase 3-beta (GSK-3b), mammalian target of rapamycin (mTOR), myoD and others to increases amino acid uptake and protein synthesis and decreases nitrogen excretion while stimulating the differentiation of satellite cells which can result in growth not only of skeletal muscle but also of internal organs such as the spleen, liver and heart. Circulating IGF-1 is produced by the liver in response to stimulation by growth hormone. IGF-1 in skeletal muscle is produced locally and stimulates hypertrophy and hyperplasia locally in what is referred to as a paracrine action. When produced locally, IGF-1 is often modified to form a slightly different protein called mechano-growth factor or MGF. Testosterone stimulation of the androgen receptor has been shown to result in local production of IGF-1 in skeletal muscle.

IGF-1 circulates in the plasma bound to a family of binding proteins. These binding proteins extend the half-life of IGF-1, which is usually very short. They also transport IGF-1 to target cells and modulate the action of IGF-1. There are six known IGF binding proteins. Under most conditions, IGF binding proteins seem to inhibit IGF-1 activity, probably by reducing the free concentrations available for binding. IGFBPs also inhibit IGF-1 activity by competing with IGF-1 receptors for IGF-1 binding. IGFBP3 can interact directly with cell membranes (possibly through a receptor of its own) to inhibit the action of IGF-1 and to exert effects of its own. IGFBP5 is widely considered to be a potentiator of IGF-1 action, probably by delivering IGF-1 to its receptor. Androgens increase IGFBP5 levels while reducing IGFBP3 levels which further suggests that IGFBP3 is a negative regulator if IGF-1 activity while IGFBP5 is a positive regulator. IGFBP4 has been shown to be an inhibitor of IGF-1 anabolic action in skeletal muscle.

It is no wonder that such a potent anabolic is being used illicitly to try to enhance muscle strength and size. Recombinant IGF-1 in various forms is available for research purposes and though it is not intended for human consumption, users have been experimenting with it for quite some time. Some have attempted to inject recombinant IGF-1 subcutaneously but the quantities needed and the short half-life result in minimal efficacy. Local intramuscular injections seem to produce some local anabolic effect but again, the short half-life limits its utility. A variant form of IGF-1 called Long R3 IGF-1 that has minimal binding to IGF binding proteins and a longer half-life has been used to promote anabolism. The down side to this particular form of IGF-1 is that it circulates at high levels in an unbound form. Circulating IGF-1 has been shown to be associated with tumor progression while IGF binding proteins (particularly binding protein 3) have been shown to protect against tumor progression, likely through restricting the actions of IGF-1. Another form of IGF-1 that has been proposed as an anabolic agent is des(1-3)IGF-1. This shortened form of IGF-1 is incapable of being bound by IGF-1 binding proteins and is much more potent in stimulating hyperplasia in skeletal muscle. Injected locally, this peptide may have better growth promoting properties than native IGF-1. The use of IGF-1, especially in a systemic fashion, will result in decreased natural production of GH.

The IGF system is complex with multiple ligands and binding proteins whose roles are not fully understood. The IGF-1/AKT pathway has been demonstrated not just to promote growth in skeletal muscle but also in internal organs and to play a role in the progression of cancer suggesting that this pathway must be carefully regulated to prevent serious side effects. The fact that these peptides are not scheduled and are available in a pseudo-legal fashion makes them much more available than AAS but with a potentially much higher liability profile. This is one of the unfortunate unintended consequences of the criminalization of AAS.

GHRP-6 and Peptide Hormone Craze

It seems everyone is raving on peptide hormones as the amazing 'new thing' in lazy, drug-induced muscle growth and fat loss. The fact is, injectable peptide hormones have been around for decades. The diabetic hormone Insulin is a peptide hormone and it was first available in the 1920's!

When Peptides Came To Fame
But Growth Hormone (GH) was the peptide hormone that changed everything. GH was credited to creating the new era of muscular bodybuilding monsters from around the time Lee Haney arrived in the 80's. And demand for the drug - and its reputation as being THE underground 'secret of the pros' - was bolstered by its mind-blowingly expensive price and rarity.

Then IGF-1 hit the black market before it was even an approved drug and the mystery and rumors surround GH, Insulin and IGF reached fever pitch. Steroids were old news. Now, if you want to look like a pro bodybuilder you just need to get enough of the right peptides.

GHRP-6
Which brings us to GHRP-6. GH Releasing Peptide is cheap and... well, currently not illegal to purchase over the internet. As the name suggests, it causes GH release; so people figure it must be exactly the same as GH and therefore will make them look like a pro bodybuilder in no time, with no effort and without all the rest of the drugs. Unfortunately, you won't look anything like a pro bodybuilder from using GHRP-6. The only reason it is so HUGELY popular is because finally Mr Average can AFFORD something that looks like the hardcore 'gear' the pro's use... except not.

I don't know anybody who got anything out of GHRP-6 whatsoever! At least, nothing over and above what might be expected from the other 'things' they were doing/taking at the time. In fact, when really pressed, nobody I know seems to know of anybody else who got any great benefit out of it either. All of the guys I know who still use it only do because it is cheap and they don't want to risk not taking it, 'in case it helps'.

So Why Use It?
Everybody knows that pro bodybuilders use lots of drugs and, these days, are as lazy as sin in the gym. The conclusion for many people is that drugs or injecting/boosting your naturally occurring hormones is the only way to build muscle.

Supplements are selling like crazy in response to the belief that the solution to an awesome physique is in a bottle. And if your muscles don't arrive you don't blame your hopeless training or disgraceful diet. You just got the wrong bottle of magic potion.

Many young guys will inject anything they possibly can afford and get and then strangely believe they are transforming into a pro bodybuilder just by being so 'hardcore' as to be taking a drug. I knew a guy who kicked in the door of his own car in a claimed 'roid rage' only minutes after injecting himself with some cooking oil that he thought was a steroid.

When Peptides Become Relevant to Bodybuilding Training
It all comes back to what I've always said: its all about your training. Train and diet properly and a drug-free athlete should be able to achieve about a 260kg deadlift before things become extremely hard to go further. If you can't get a natural 260kg deadlift then you are training and eating wrong. Some guys can even acheive a 260kg deadlift without ever actually doing a deadlift or training hard!

But if the physique of a lean 260kg deadlifter is not muscular enough for you (eg typically around 95kg at 8% bodyfat at 180cm) then you are going to probably need unnatural means to achieve your unnatural goals. Very low dose, testosterone optimisation therapy can help a successfully training athlete to achieve a 300kg deadlift and a great physique (eg around 105kg at 8% at 180cm).

If you still want more unnatural levels of muscle then you probably need to break the law and cycle higher doses of testosterone and/or add GH. Beyond a 340kg deadlift (growing bigger than around 115-125kg at 8% at 180cm) you'll probably need to stay on higher doses of steroids year round.

By the time you reach the muscularity capable of a 360kg deadlift (ie over 130kg, lean at 180cm) as a career-criminal steroid user, then progress will probably be determined by cycles of insulin with GH and IGF-1 and all the rest.

This is the point at which these peptide growth factors become relevant: the pro-bodybuilder level. Without the heavy base of steroid hormones, though, they are a mostly a waste of time and money. And if you are already using all of these drugs to achieve a lesser physique then you need to take a serious look at yourself, your diet and your training!

ACTIONS OF DIFFERENT ESTERS

There are many different esters that are used with anabolic steroids / androgenic steroids, but again, they all do basically the same thing. Esters vary only in their ability to reduce a steroid's water solubility. An ester like propionate for example will slow the release of a steroid for a few days, while the duration will be weeks with a decanoate ester. Esters have no effect on the tendency for the parent steroid to convert to estrogen or DHT (dihydrotestosterone: a more potent metabolite) nor will it effect the overall muscle-building potency of the compound. Any differences in results and side effects that may be noted by bodybuilders who have used various esterified versions of the same base steroid are just issues of timing. Testosterone enanthate causes estrogen related problems more readily than Sustanon, simply because with enanthate testosterone levels will peak and trough much sooner (1-2 week release duration as opposed to 3 or 4). Likewise testosterone suspension is the worst in regards to gyno and water bloat because blood hormone levels peak so quickly with this drug. Instead of waiting weeks for testosterone levels to rise to their highest point, here we are at most looking at a couple of days. Given an equal blood level of testosterone, there would be no difference in the rate of aromatization or DHT conversion between different esters. There is simply no mechanism for this to be possible.

There is however one way that we can say an ester does technically effect potency; it is calculated in the steroid weight. The heavier the ester chain, the greater is its percentage of the total weight. In the case of testosterone enanthate for example, 250mg of esterified steroid (testosterone enanthate) is equal to only 180mg of free testosterone. 70mgs out of each 250mg injection is the weight of the ester. If we wanted to be really picky, we could consider enanthate slightly MORE potent than cypionate (I know this goes against popular thinking) as its ester chain contains one less carbon atom (therefore taking up a slightly smaller percentage of total weight). Propionate would of course come out on top of the three, releasing a measurable (but not significant) amount more testosterone per injection than cypionate or enanthate.

WHAT AN ESTER IS, AND HOW IT WORKS

If you have taken an interest in anabolic steroids you have noticed the similarities on the labeling of many drugs. Let's look at testosterone for example. One can find compounds like testosterone cypionate, enanthate, propionate, heptylate; caproate, phenylpropionate, isocaproate, decanoate, acetate, the list goes on and on. In all such cases the parent hormone is testosterone, which had been modified by adding an ester (enanthate, propionate etc.) to its structure. The following question arises: What is the difference between the various esterified versions of testosterone in regards to their use in bodybuilding?

An ester is a chain composed primarily of carbon and hydrogen atoms. This chain is typically attached to the parent anabolic steroid at the 17th carbon position (beta orientation), although some compounds do carry esters at position 3 (for the purposes of this article it is not crucial to understand the exact position of the ester). Esterification of an injectable anabolic/androgenic steroid basically accomplishes one thing, it slows the release of the parent steroid from the site of injection. This happens because the ester will notably lower the water solubility of the steroid, and increase its lipid (fat) solubility. This will cause the drug to form a deposit in the muscle tissue, from which it will slowly enter into circulation as it is picked up in small quantities by the blood. Generally, the longer the ester chain, the lower the water solubility of the compound, and the longer it will take to for the full dosage to reach general circulation.

Slowing the release of the parent steroid is a great benefit in steroid medicine, as free testosterone (or other steroid hormones) previously would remain active in the body for a very short period of time (typically hours). This would necessitate an unpleasant daily injection schedule if one wished to maintain a continuous elevation of testosterone (the goal of testosterone replacement therapy). By adding an ester, the patient can visit the doctor as infrequently as once per month for his injection, instead of having to constantly re-administer the drug to achieve a therapeutic effect. Clearly without the use of an ester, therapy with an injectable anabolic/androgen would be much more difficult.

Esterification temporarily deactivates the steroid molecule. With a chain blocking the 17th beta position, binding to the androgen receptor is not possible (it can exert no activity in the body). In order for the compound to become active the ester must therefore first be removed. This automatically occurs once the compound has filtered into blood circulation, where esterase enzymes quickly cleave off (hydrolyze) the ester chain. This will restore the necessary hydroxyl (OH) group at the 17th beta position, enabling the drug to attach to the appropriate receptor. Now and only now will the steroid be able to have an effect on skeletal muscle tissue. You can start to see why considering testosterone cypionate much more potent than enanthate makes little sense, as your muscles are seeing only free testosterone no matter what ester was used to deploy it.