Wednesday, August 31, 2011

Growth Hormone Two

Here is an interesting piece by Anthony Roberts. I know that there are dozens if not hundreds of GH variants in mammalia physiology, but this piece smacks of commercial interest! I'll keep you posted.


Growth Hormone Two (20kDa Growth Hormone)
Posted by Anthony Roberts
Aug 28, 2011

Synthetic Growth hormone, alternately known as rhGH, is the 22kDa isomer of the growth hormone found naturally within the human body (kDa denotes kilo dalton, a measure of mass on the atomic scale). It has increasingly been called “Growth Hormone 1″ in emerging scientific literature, out of respect for the characterization of other isomers of GH. Each isomer of growth hormone is a distinct chemical species comprised of both the same number and types of atoms as the other isomers, but possessing different properties. The products being sold by every pharmaceutical company in the world for the use of treating growth hormone deficiency (the same stuff being used by athletes and bodybuilders) is the 22kDa isomer.

* Fig. 1. Ba/F3-hGHR Cell Proliferation Caused by 22K- or 20K-hGH , Molecular Endocrinology January 1, 1998 vol. 12 no. 1 146-156
But there is another form, currently available, known as GH2 or Growth Hormone Two…and it is comprised of the 20kDa isomer of Growth Hormone (there are numerous other isoforms of the Growth Hormone protein as well). The 20,000 dalton human GH (20kDa-hGH) is a naturally occurring isoform of the 22,000 dalton hGH (22K-hGH) and constitutes roughly 5–10% of pituitary- hGH and roughly 6% of serum hGH. Both arise from the same gene albeit by alternative mRNA splicing, and the 20-version differs from the 22 in its deleted amino acid region (E32-Q46). Interestingly, GH2 (the 20k version) appears to show a greater absorption rate in some cells, when compared to regular GH.
The currently available growth hormone doping test used by the World Anti-Doping Agency relies on the ratio of 20:22kDa. Using standard rhGH will elevate an athlete’s 22kDa levels while lowering the 20kDa level. This depressed state of the latter isoform compared to the elevated state of the former, is the litmus test by which a sample is said to be positive for growth hormone use. However, GH2 use can elevate this isoform, thereby manipulating the ratio, and can therefore be used as a fool-proof masking agent for growth hormone against the current WADA test.
Additionally, it appears that GH2 is less prone to being bound up by hGH-Binding Proteins, and therefore able to exert a stronger effect than regular hGH on tissues that release hGH-BP. For example, human abdominal fat tissues have has a high hGH-BP level in healthy nonobese adults, so it may be possible that GH2 is more potent for fat loss in this area. additionally, GH2 seems to have a longer clearance time (PMID: 19467614), perhaps due to its lower affinity to binding proteins, or through a lowered impact on the GH-axis negative feedback loop.
Growth hormone exerts some of its direct actions through stimulating site-specific cell surface receptors (Nature 1987; 330: 537–43), but most of its anabolic actions are mediated through the generation of IGF-1 (Endocrinology 1988; 123: 433–7), which has has highly pronounced anabolic effects and is responsible for profound metabolic changes in numerous cell types (Endocr Rev 1995; 16: 3–34) The anabolic effects of Growth Hormone 1, therefore, are thought to be mediated, if not caused outright or strongly attributable to, Insulin-like Growth Factor 1.
It’s important to remember that the effects of GH are largely reliant on IGF-1 expression, because Growth Hormone Two (GH2) has shown similar, if not greater, ability to stimulate the production of IGF-1. In addition, the lipolytic (fat-burning) effects are also thought to be largely a result of increased IGF-1 levels, and not as a direct result of GH elevation, per se.

The solid dots equal placebo, the empty dots are.1mg/kg of 20kDa-GH (GH2), and the lines in between correspond to varying other doses, from low to high producing corresponding IGF-1 increases.
In a study published by The Journal of Clinical Endocrinology & Metabolism (Feb. 1, 2000, vol. 85 no. 2, pgs 601-606), GH2 was administered to normal men (20–31 yr of age, n= 6–8 per group), achieving an elevation in 20kDa-hGH levels that increased in a dose-dependent manner while suppressing 22kDa-hGH secretion [administration of regular rhGH (GH1) has the opposite effect, i.e. it lowers the natural secretion of 20kDa-hGH]. Moreover, this study also demonstrated that GH2 significantly elevates insulin-like growth factor 1 levels. According to the scientists: “These results suggested that: 1) regulation of 20K-hGH secretion is physiologically the same as that of 22K-hGH; 2) the pharmacokinetics after sc injection of 20K-hGH are comparable with those of 22K-hGH; 3) 20K-hGH regulates hGH secretion through “GH-induced negative feedback mechanisms”; and 4) administration of 20K-hGH is expected to exert GH actions (growth-promoting activity and lipolytic activity).”
As you can see from the chart on the right, the highest dose of GH2 corresponded to an IGF-1 elevation several orders of magnitude exponentially greater than placebo. Free Fatty acids also increased, and these increases in the main hGH-dependent substances (i.e. FFA and IGF-I) suggested that 20K-hGH has direct GH actions on adipose tissue or the liver through hGH receptors that appear very similar, if not exactly similar, to 22K-hGH (GH1).
However, some of the available literature would indicate that lower concentrations of 20kDa-hGH more strongly induces muscular IGF-I (mIGF-1) gene expression as compared to the 22kDa-hGH isomer (at least in mice):

(PMID: 10890180)
Furthermore, if we compare the elevation in IGF-1 levels seen in the previous charts it starts to become apparent that GH2 may actually be more anabolic than regular rhGH, although it needs to be noted that the stronger effect of 20K hGH than that of 22K hGH in enhancing the IGF-I gene expression may be correlated with a yet-undescribed 20K hGH specific receptor dimerization process. (PMID: 10890180) So although the previous chart is from a rodent model, it would give us good reason to think that there is strong potential for GH2 to be more anabolic than regular GH, or at least equal at a lower dose. Another study, performed on humans, from 2004, tells us that GH2 can be used successfully for Growth Hormone replacement therapy in GH deficient adults (The Journal of Clinical Endocrinology & Metabolism 89(4):1562–1571 )
Summarily reviewing the currently available data, GH2 has a longer active life in the human body than currently available rhGH, it has a stronger impact on IGF-1 levels and therefore a potentially higher anabolic effect, or at least the same anabolic effect at a considerably lower dose. Oh…and it’s not too expensive, either…