Tag Archives: IGF-1

Androgen receptor

The Truth About “Down Regulation”

by Ed Barillas, Staff Writer

There is as much disinformation and misinformation about steroids as there is good and solid information among bodybuilders. If you step into any gym you will likely hear some kid yacking to his buddies about how steroids do this or how they do that – you get the picture. Anyway, this soon starts somewhat of a pissing contest as to who knows more about steroids and has about the same kind of imbicilic banter that teenage boys get into about girls and sex. With steroid banter, you hear all the popular terms like Deca, Test, HGH, gyno, zits, raisins, roid, freak, monster, roid-rage, but if by some rare chance they are smart and have been reading this or some other high quality bodybuilding site on the net and in our forums, they may actually get a few details right. More often than not they know just enough to be dangerous. Fortunately, steroids have not proven to be all that dangerous and not only that, most of these guys who are infatuated with steroids will not ever use or even see them other than in magazines.

Androgen receptor

A human androgen receptor (AR)

This kind of ego driven gym talk does not really bother me until they begin giving advice to other clueless people who actually have access to them and that’s where the problems begin. Spewing out steroid lingo gives other less experienced kids the impression that these kids actually know what they are talking about. That is how all of the psuedo-science folklore about steroids perpetuates. This is also why most people who actually use steroids know little about them and this last fact should bother anyone who cares about bodybuilding and/or bodybuilders.

The game plan of this article is to tell you about what Androgens actually do and how this precludes Androgen receptor down regulation. One misunderstood common principle of steroid physiology is the concept of Androgen receptors (AR), sometimes called “steroid receptors”, and the effects of steroid use on their regulation. It is commonly thought that taking Androgens for extended periods of time will lead to what is called AR “down regulation.” The notion for this argument goes something like this – when using steroids during an extended cycle, you eventually stop growing, even though the dose has not decreased. This belief has persisted despite the fact that there is no scientific evidence to date that shows that increased levels of Androgens down regulates the Androgen receptor in muscle tissue.

One can say that AR down-regulation sounds pretty straightforward on the surface. After all, we know that receptor down-regulation happens with other messenger-mediated systems in the body such as adrenergic receptors. It has been shown many a times that when taking a beta agonist such as Clenbuterol, the number of beta-receptors on target cells begins to lower. This is due to a decrease in the half-life of receptor proteins without a decrease in the rate that the cell is making new receptors. This leads to a decrease in the potency of a given dose. As a result, with fewer receptors you get a smaller, or lower, physiological response. This is a natural way for your body to maintain equilibrium in the face of an unusually high level of beta-agonism.

But really this example using Clenbuterol is not an appropriate one. Androgen receptors and adrenergic receptors are very different. Nevertheless, this is the argument for Androgen receptor down-regulation and the reasoning behind it. The differences in the regulation of ARs and adrenergic receptors, in part, show the mistake in the view that AR down-regulate when you take steroids. Where adrenergic receptor half-life is lowered in most target cells with increased catecholamines, AR receptors half-lives are actually increased in many tissues in the presence of Androgens.

If I may show you the flip side to this coin, against AR down-regulation in muscle tissue, I feel that once you consider all of the effects of testosterone on muscle cells you come to realize that when you eventually stop growing it is not because there is a reduction in the number of Androgen receptors.

So how do anabolic steroids produce muscle growth? The basic common answer is that steroids increase protein synthesis. Which is true, but there is more to it than simple increases in protein synthesis. Actually, the answer to the question of how steroids work must include virtually every mechanism involved in skeletal muscle hypertrophy which mechanisms include: Enhanced protein synthesis, enhanced growth factor activity (e.g. GH, IGF-1, etc.), ½ Enhanced activation of myogenic stem cells (i.e. satellite cells) ½ Enhanced myo-nuclear number (to maintain nuclear to cytoplasmic ratio) and ½ New myo-fiber formation.

Starting with enhanced growth factor activity, we know that testosterone increases HGH and IGF-1 levels. In a recent study the effects of testosterone and stanozolol were compared for their effects on stimulating HGH release. Testosterone enanthate (only 3 mg per kg per week) increased HGH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol (0.1mg per kg per day) had zero effect whatsoever on IGF-1 or HGH levels. This study was only 3 weeks long, and although stanozolol did not affect HGH or IGF-1 levels, it had the same effect on urinary nitrogen levels. So what does this difference in the effects of testosterone and stanozolol mean? It means that stanozolol may increase protein synthesis by binding to AR receptors in existing myonuclei, but because it does not increase growth factor levels, it is much less effective at activating satellite cells and therefore may not increase satellite cell activity nor myo-nuclear number directly when compared to testosterone esters.

 

 

 

ARod

A-Rod’s Advanced Drug Regimen

Although Alex Rodriguez finally waived the flag of surrender and dropped his lawsuit against the MLB for suspending him, we have learned quite a bit about the evidence the league had on the star player’s use of performance enhancing drugs.

ARod

Alex Rodriguz’ PED program created by Biogenesis was a high-priced mix of high-tech drugs.

According to documents the league obtained from Bioigenesis, the lab where Rodriguez and a slew of other baseball players went for their PEDs,  Rodriguez’s $12,000 per month drug regimen appears to utilize some of the most sophisticated drugs and diet programs in use today. In four distinct, month-long phases, Rodriquez’s cycle included hGH, GHRP, CJC, Testosterone cream, L-Glutathione cream, Melatonin, Testosterone Troche, Clomiphene, iGF-1, hCG and a host of other vitamins, omegas and other dietary supplements.

Tony Bosch, Biogenesis owner and the developer of this high-priced program, likely got most of the drugs for these programs from legitimate drug-makers through his father Pedro Bosch who is a family physician and was listed as Biogenesis’ medical director. However, some of the drugs in the list were likely procured through underground labs because investigational compounds like GHRP 2/6 are not available on any regulated market.

“My guess is that [Biogenesis] was getting them from [online sources] and administering and reselling it to [Rodriguez],” said Jose Garcia, MD, PhD, an endocrinologist at Baylor College of Medicine who has been involved in studies of GHRP 2/6 in an interview with MedPage Today. “You would never go to a site like this because there is no quality control so you never know if these products are contaminated or if they contain what they’re supposed to. Not even for animal experiments.”

Tony Bosch

In exchange for immunity from lawsuits brought on by the MLB against Biogenesis and its associates, Tony Bosch turned over the evidence that eventually sunk Rodriguez.

Despite Dr. Garcia’s adamant plea for people to stop taking these kinds of drugs, they are known to the bodybuilding community as some of the best advances in lowering unwanted levels of estrogen during a testosterone cycle. But just as the hefty price tag for Biogenesis’ PED program indicates, these drugs can be very expensive.

As for Rodriguez, the most expensive part of his drug program will be his 162-game suspension from MLB which will take him out of the 2014 season completely – without pay.

As for Tony Bosch, now that Rodriguez has dropped all of his lawsuits against MLB, his players’ union and everyone else he threatened to sue over his getting caught, it looks like MLB will drop its own lawsuit against the Biogenesis founder on the grounds that he and his associates committed “intentional and unjustified tortious interference” with contracts between MLB and its players by providing them with banned substances.

It was MLB’s threat of litigation that forced Bosch to hand over information on Rodriguez and other baseball players who were using PEDs from Biogenesis, which is how the information on Rodriguez’ drug regimen (see below) was released.

Alex Rodriguez’ Drug Regimen

arod drug regimen

hexarelin12

Hexarelin

Hexarelin

L-Histidyl-2-methyl-D-tryptophyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide; Examorelin

Molecular Formula C47H58N12O6
Molecular Weight 887.04
CAS Registry Number 140703-51-1

hexarelin12Hexarelin is a six-amino acid peptide.  Studies have shown that hexarelin is actually more effective and longer lasting than growth hormone releasing hormone (GHRH).  It is also known that GHRP-6 has a synergistic effect with GHRH, causing a far greater release than either of these substances alone.  By combining GHRP-6 with Hexarelin, a more potent GH releasing peptide combination is created than ever heard of. The potential clinical usefulness of these GH releasing hexapeptides is also reinforced by observations that long-term administration produces elevations in circulating IGF-1 concentrations.  Long term treatment with GHRP-6 similarly has been shown to elevate serum IGF-1 as well as IGF-binding protein-3 concentrations and promote linear growth.

amber_amps_2

MGF an alternatively spliced variant of IGF-1

picture of amber_amps

MGF C-terminal peptide provided very significant protection to the vulnerable neurons.

 

The ischemic stroke is the third leading cause of death in developed countries. The C-terminal peptide of mechano-growth factor (MGF), an alternatively spliced variant of insulin-like growth factor 1 (IGF-1), was found to function independently from the rest of the molecule and showed a neuroprotective effect in vivo and in vitro. In vivo, in a gerbil model of transient brain ischemia, treatment with the synthetic MGF C-terminal peptide provided very significant protection to the vulnerable neurons. In the same model, ischemia evoked increased expression of endogenous MGF in the ischemia-resistant hippocampal neurons, suggesting that the endogenous MGF might have an important neuroprotective function. In an in vitro organotypic hippocampal culture model of neurodegeneration, the synthetic peptide was as potent as the full-length IGF-1 while its effect lasted significantly longer than that of recombinant IGF-1. While two peptides showed an additive effect, the neuroprotective action of the C-terminal MGF was independent from the IGF-1 receptor, indicating a new mode of action for this molecule. Although MGF is known for its regenerative capability in skeletal muscle, our findings demonstrate for the first time a neuroprotective role against ischemia for this specific IGF-1 isoform. Therefore, the C-terminal MGF peptide has a potential to be developed into a therapeutic modality for the prevention of neuronal damage. Dluzniewska J, et al. FASEB J. 2005 Sep 6; [Epub ahead of print]


Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation

The physiological function of a recently cloned splice variant of insulin-like growth factor-I (IGF-I; mechano growth factor (MGF)) was studied using an in vitro cell model. Unlike mature IGF-I, the distinct E domain of MGF inhibits terminal differentiation whilst increasing myoblast proliferation. Blocking the IGF-I receptor with a specific antibody indicated that the function of MGF E domain is mediated via a different receptor. The results provide a basis for localized tissue adaptation and helps explain why loss of muscle mass occurs in the elderly and in dystrophic muscle in which MGF production is markedly affected.

Yang SY, Goldspink G. FEBS Lett. 2002 Jul 3;522(1-3):156-60.