Synthetic GH (aggregation) One reason for problems w/ synthetic GH

[DatBtrue]

Previously posted on my board.

Therapeutic Peptides and Proteins Formulation,
Processing, and Delivery Systems,Second Edition,
Ajay K. Banga, Ph.D.,
CRC Press 2006​

This underscores some of the problems with the long-chain complex structure of synthetic GH and touches on why people in part experience a wide variety of experiences concerning effectiveness and red welts.

Aggregation

Protein molecules can often undergo self-association by physical or chemical forces to form dimers, trimers, tetramers, or higher oligomers. This self-association or aggregation is a common problem during formulation development and pharmaceutical processing. Although aggregation is physical instability, it can lead to loss of biological activity. However, some proteins may exert their biological effects as a dimer, trimer, or higher oligomeric forms and may lose biological activity on dissociation. For instance, tumor necrosis factor exists as a compact trimer in aqueous solutions, and maintenance of its trimeric structure is essential for its activity. In any case, a study of the aggregation phenomena is crucial to developing a successful peptide or protein formulation. Even if aggregation does not result in loss of bioactivity, formation of insoluble aggregates can cause blockage of tubing, membranes, or pumps in an infusion set, as is the case with insulin. Furthermore, because aggregation leads to an increase in effective molecular weight, the aggregated protein may be more immunogenic.

[To be clear here, aggregation may be responsible for the ability of a particular substance, to provoke an immune response... such as is sometimes seen w/ black market GH]

Aggregation behavior of human growth hormone

The hGH can undergo aggregation to form a dimer or higher molecular weight oligomers. Such aggregation can take place during formulation, processing, storage, and reconstitution. Phenolic compounds also induce aggregation of hGH. The most common aggregation product is a stable, noncovalent dimer that is chemically identical to hGH but is essentially inactive in bioassay. Zinc ions (Zn2+) can also induce dimerization of hGH. Two Zn2+ ions associate per dimer of hGH, and the formation of the Zn2+–hGH dimeric complex may be important for the storage of hGH in secretory granules. Replacement of potential Zn2+ ligands such as His18, His21, and Glu174 in hGH with alanine has been reported to weaken Zn2+ binding, thereby preventing formation of hGH dimer. Aggregation of hGH was known to be a problem during its preparation from pituitary gland before the availability of the recombinant protein. A process of ultrafiltration was shown to result in an aggregate-free preparation. Aggregation of hGH can be induced by freezing and thawing or by agitation. Product literature of recombinant hGH from Eli Lilly (Humatrope) instructs to reconstitute the lyophilized powder by injecting the diluent against the glass wall and mixing by gentle swirling, without any shaking. As currently formulated, hGH readily precipitates out of neutral solution with vigorous mixing. Besides stability and bioactivity considerations, any aggregation of hGH may increase the antigenicity of the product.

[To be clear aggregation of GH has the capacity to stimulate the production of antibodies or the capacity to react with an antibody.]

 

[jm425]

Interesting read bro. Are you saying that all synthetic gh of 191aa sequence, can eventually lead to the body producing antibodies?

 

[123cctv]

Interesting read bro. Are you saying that all synthetic gh of 191aa sequence, can eventually lead to the body producing antibodies?

That's a bit extreme - though the manufacturing process is key in the creation/formation or lack thereof.

Findings of antibodies being formed are dependant and noted via different manufacturers. Refer to GenSci's referred stats and studies:
**broken link removed**

Note: Nutropin™, Saizen™, Humatrope™, Jintropin™, Genotropin™ displayed a percentage rate of developing hGH antibodies from 0 to 1.9% - very low!


GenSci also mentions in their FAQ:
**broken link removed**

"What’s the consequence of using low quality cheap hGH brand or 192 amino acid hGH?

Most low quality cheap hGH brands does contain hGH, but they also contain lots of E.coli host protein contamination. When injected (or when you injected 192 amino acid hGH), you would feel the hGH function, but in the meantime, your body will quickly generate antibodies to hGH. In a few months, your body’s hGH will stop functioning, and any new injection of hGH will be useless . Therefore it is key to always stick to the highest quality hGH..."

 

[jm425]

That's a bit extreme - though the manufacturing process is key in the creation/formation or lack thereof.

Findings of antibodies being formed are dependant and noted via different manufacturers. Refer to GenSci's referred stats and studies:
**broken link removed**

Note: Nutropin™, Saizen™, Humatrope™, Jintropin™, Genotropin™ displayed a percentage rate of developing hGH antibodies from 0 to 1.9% - very low!


GenSci also mentions in their FAQ:
**broken link removed**

"What’s the consequence of using low quality cheap hGH brand or 192 amino acid hGH?

Most low quality cheap hGH brands does contain hGH, but they also contain lots of E.coli host protein contamination. When injected (or when you injected 192 amino acid hGH), you would feel the hGH function, but in the meantime, your body will quickly generate antibodies to hGH. In a few months, your body’s hGH will stop functioning, and any new injection of hGH will be useless . Therefore it is key to always stick to the highest quality hGH..."

Bro, all of us would love to use pharm grade gh. However, not all of us have access to them.

 

[123cctv]

Bro, all of us would love to use pharm grade gh. However, not all of us have access to them.

Ah, I see what you're saying. However, while Dat's article commented briefly re: non pharm grade, i.e. Black Market GH...

"aggregation may be responsible for the ability of a particular substance, to provoke an immune response... such as is sometimes seen w/ black market GH]"

....the article appears to be covering GH in general which includes both Black Market as well as legit pharm grade. At any rate, since the article is mentions both -- so did I.

By the way, if you (jm425 and only you) ever need any help w/pharm grade GH - leme know.

 

[Kaladryn]

That's a bit extreme - though the manufacturing process is key in the creation/formation or lack thereof.

Findings of antibodies being formed are dependant and noted via different manufacturers. Refer to GenSci's referred stats and studies:
**broken link removed**

Note: Nutropin™, Saizen™, Humatrope™, Jintropin™, Genotropin™ displayed a percentage rate of developing hGH antibodies from 0 to 1.9% - very low!


GenSci also mentions in their FAQ:
**broken link removed**

"What’s the consequence of using low quality cheap hGH brand or 192 amino acid hGH?

Most low quality cheap hGH brands does contain hGH, but they also contain lots of E.coli host protein contamination. When injected (or when you injected 192 amino acid hGH), you would feel the hGH function, but in the meantime, your body will quickly generate antibodies to hGH. In a few months, your body’s hGH will stop functioning, and any new injection of hGH will be useless . Therefore it is key to always stick to the highest quality hGH..."

That GenSci crap is completely biased and obviously BS. "E.coli" lol

 

[DatBtrue]

That GenSci crap is completely biased and obviously BS. "E.coli" lol

You do understand that that is how growth hormone is made don't you? Hmmm.... I don't think you do.

Escherichia coli and other bacteria are genetically engineered to produce some peptides. Growth Hormone is a peptide made this way. The human growth hormone gene is spliced into a plasmid which is inserted into the bacteria where it makes growth hormone

The GHRHs and GHRPs are not made this way. They are made via Solid State Synthesis.

 

[123cctv]

That GenSci crap is completely biased and obviously BS. "E.coli" lol

Your response carries with it no fact or other reference? Why not consider the GH manufacturing companies GenSci sited? They certainly, by no means lack the financial resources to seek legal recourse if GenSci is promoting lies.

Remember, GenSci named the studies and references:

① Genotropin™ PI, Humatrope™ PI, Saizen™ PI, Nutropin™ and Nutropin AQ™ PI;
② Pan Huiru,Chen Jiqing, Zhang lina, et al. Effect of treatment of growth hormone deficiency with domestic recombinant human growth hormone.J Appl Clin Pediatr, September 2001,Vol. 16 No.5.
③ Yu Yerong, Pan Huiru, Wang Defen, et al. Clinical research of treatment of growth hormone deficiency with domestic recombinant human growth hormone. Chin J Endocrinol Metab, April 1999, Vol 15, No.2.
④ Qin Shuwen, Shi Yifan, Wang Defen, et al. A prospective study of therapeutic effect of recombinant human growth hormone in idiopathic growth hormone deficient children before adolescence. Chin J Endocrinol Metab, February 1999, Vol 15, No. 1.


So to sum up, your point is -- GenSci website is either promoting fraudulent material OR sighting biased studies? If they're lying, what about? Jintropin really forms more antibodies than they're claiming? Or Genotropin, Humatrope, Saizen, etc. really form more or less than mentioned??

All of this is *reaching* if you ask me.

Personally, if it were my company (yeah, I have one) I'd find materials that furthered my cause and promoted my product. Perhaps that's what GenSci did?

 

[MrCyp]

So maybe its best to take a month off GH every 5 or 6months on to avoid the antibodies?

 

[123cctv]

So maybe its best to take a month off GH every 5 or 6months on to avoid the antibodies?

Should let Dat chime in here - tis his thread and data. However if I may? Your solution isn't quite that simple. The development of antibodies is simply that = antibodies formed to ward off and ultimately destroy foreign organisms. Once certain antibodies are formed, they'll remain there waiting for that substance to strike again. Thus (as I see it), your choices are:

1. Use low quality GH, but don't bother holding your breath! I don't believe I'm over stepping this either. For instance, there's much low quality GH's being made! Many of these promote the formation of antibodies IF GenSci's sighted studies are even slightly accurate. To explain...

If you'll note in the link again ( **broken link removed** ) GenSci is only naming and comparing itself to legitimate pharmaceutical grade competition! Did you get that? In fact, according to the mentioned studies, LEGIT Hygetropin creates anitbodies in 2 out of 10 users and it only gets worse from there! The last two labs mentioned promote antibodies in 4 out of every 10 users!!

So what am I saying?? Can you imagine what black market GH causes? In other words, do you think the best black market GH is comparable to any legit lab? If so, to which?


2. If antibodies develope, up your dosages. However regrettably, this will be short lived as the body will counter your increased doses with the formation of increased antibodies.


3. Or, as GenSci points out, stay away from low grade synthetic GH! There are people who've used **quality** GH for years with no ill effects or notable antibody formation. I'm one of them.

 

[MAINEVENT]

Would this immunogenic response possibly be responsible for chronic reoccuring tendonitis?

 

[MrCyp]

I wonder if there is anyway or anything to take to counter the antibodies from forming in the 1st place?

 

[disgraziato]

Lets not miss the factors which can induce aggregation guys...its not a constant or a guarantee that you'll make antibodies....ie:frequent freeze thaws, ove-agitation, reconstituting directly on top of your lypholized powder, etc...there are instructions which most of us already ar aware of which can reduce the chance of aggregation hence reducing the chance that our immune system will attack our hgh.....know your source first, then know your shit.

 

[jm425]

I wonder if there is anyway or anything to take to counter the antibodies from forming in the 1st place?

I'm thinking maybe immunosuppressants like cellcept and prograf may lower the chances of antibodies forming. Not 100% sure though. I don't advocate anyone taking immunos though because they make you feel like shit and inhibit/slow down your body from fighting infection. I know from personal experience. As a liver transplant patient I have to take cellcept and prograf everyday in order to survive.

 

[Kaladryn]

You do understand that that is how growth hormone is made don't you? Hmmm.... I don't think you do.

Escherichia coli and other bacteria are genetically engineered to produce some peptides. Growth Hormone is a peptide made this way. The human growth hormone gene is spliced into a plasmid which is inserted into the bacteria where it makes growth hormone

The GHRHs and GHRPs are not made this way. They are made via Solid State Synthesis.

Interesting, I did some reading and now I'm more informe about GH made through e.coli secretion. However, I still feel that website is totally biased, and using rather flimsy scare tactics to promote their brand.

 

[123cctv]

However, I still feel that website is totally biased, and using rather flimsy scare tactics to promote their brand.

You're doing it again. No facts or point of reference. I don't even know how to reply or where to begin in addressing this type of vagueness.

You say the site's biased. OK, that's one thing I won't rebut. My website is biased to my company as well. No news here. However I don't post false/fraudulent data to further sales. Yet are you suggesting GenSci is?

Or, the data and studies GenSci lists, they're biased? If so, then to whom are these studies biased to? The entire GH industry? Remember the studies sighted included other GH manufacturers (Nutropin, Humatrope, Saizen, Genotropin, etc.). You're suggesting the data listed regarding them was altered? In other words, they didn't really form antibodies in the claimed percentages?

Or -->> the data listed is biased only to GenSci? If to GenSci only, then the other listed data regarding the other companies is what...???? Right?? Wrong?? This will be interesting. Please be specific!

Saying you "feel"..."That GenSci crap is completely biased and obviously BS." without any reference or facts, carries with it about as much weight as does saying, ""E.Coli" lol"

 

[ericraven2003]

Interesting, I did some reading and now I'm more informe about GH made through e.coli secretion. However, I still feel that website is totally biased, and using rather flimsy scare tactics to promote their brand.

And you base this on what? Come on now.

 

[Quad-smack]

Interesting read.
At Gensci's web site, they have supposedly done research showing antibody formation in response to GH administration. Jintropin supposedly has the lowest rate of antibody formation of Pharm grade GH on the market.
**broken link removed**

 

[123cctv]

Interesting read.
At Gensci's web site, they have supposedly done research showing antibody formation in response to GH administration. Jintropin supposedly has the lowest rate of antibody formation of Pharm grade GH on the market.
**broken link removed**

Yes, that is a very interesting read. However the Jintropin GenSci is referring to on this page, is Jintropin AQ. It's a liquid, not powder and remains in a liquid state throughout the manufacuring process -- unlike the powder form most of us use.

They stated,

"Jintropin™ AQ has better clinical effect and lower antibody formation.

Normal lyophilized powder rhGH, because it contains trace amount of rhGH aggregates, would always generate slight amount of rhGH antibodies in small percentage of people (about 1-2% of the people). Antibodies to rhGH will compromise the long term benefit of rhGH. Beware of antibodies to hGH. However, Jintropin™ AQ doesn't cause any formation of antibodies because it contains absolutely no rhGH aggregates."

FYI - The Jintropin AQ 150IU kit (w/5 30IU vials) cost approx 950USD. That's 6.35 per IU. Not cheap, but probably worth it.

 

[jm425]

Yes, that is a very interesting read. However the Jintropin GenSci is referring to on this page, is Jintropin AQ. It's a liquid, not powder and remains in a liquid state throughout the manufacuring process -- unlike the powder form most of us use.

They stated,

"Jintropin™ AQ has better clinical effect and lower antibody formation.

Normal lyophilized powder rhGH, because it contains trace amount of rhGH aggregates, would always generate slight amount of rhGH antibodies in small percentage of people (about 1-2% of the people). Antibodies to rhGH will compromise the long term benefit of rhGH.Beware of antibodies to hGH. However, Jintropin™ AQ doesn't cause any formation of antibodies because it contains absolutely no rhGH aggregates."


Back when I could afford it, I used the Nutropin Pen (it too remains in liquid form) for approx 6 months and noticed a very nice bodily transformation.

FYI - The Jintropin AQ 150IU kit (w/5 30IU vials) cost approx 950USD. That's 6.35 per IU. Not cheap, but probably worth it.

6.35 dollars per iu?! That's fuckin' insane!!!