# STEROIDS FORUM > IGF-1 LR3, HGH, and INSULIN QUESTIONS >  Why/how is gynecomastia an HGH side effect?

## Polska

Gyno is listed as a side effect of HGH and some guys have reported getting it. How is this possible if GH has no androgenic properties?

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## Deep_Fried

Hey,

The reason is that HGH and Prolactin belong to the same superclass of cytokines and exhibit similarities in their structure.

This results in the fact that HGH has a good binding affinity for the Prolactin receptor and therefore can mediate the same signaling (lactogenesis)that Prolactin would, at the site of mammary tissue PRL receptors.

Here are 2 threads with similar responses from me:

http://forums.steroid.com/showthread.php?t=369626
http://forums.steroid.com/showthread.php?t=365728

Hope this helped shed some light  :Wink:

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## Slide

Thanks Deep Fried that is some great info. 

So is prolactin Gyno permanent? if you stop the HGH will it go back down or no?

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## Flex-Appeal

So an easy way to prevent this would be say.... cabergoline correct?
Or would this have a negative effect on the growth hormone ...?

Im just happy as hell i don't have gyno issues... especially with hgh

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## Flex-Appeal

> Thanks Deep Fried that is some great info. 
> 
> So is prolactin Gyno permanent? if you stop the HGH will it go back down or no?


If gyno is created and grows, it can be reduced (with drugs) in size but from what i have read it will always be there unless you have surgery to correct your problem.

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## Slide

yes but does prolactin gyno cause growth of the tissue or just puffy sensitive nipples?

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## Garbanzo Dude

vitamin b6 100mgs and more can help fight prolactin also,,,, but in a bad situation caber!

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## Swifto

> yes but does prolactin gyno cause growth of the tissue or just puffy sensitive nipples?


It will contribute to growth, I believe. Although there is no evidence ANY androgen has increased PRL, even 19-Nor's.

Although the main culprit is Estrogen. ERalpha mediates proliferation.

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## Deep_Fried

> So an easy way to prevent this would be say.... cabergoline correct?
> Or would this have a negative effect on the growth hormone ...?
> 
> Im just happy as hell i don't have gyno issues... especially with hgh



Dopamine Agonists (Cabergoline, Bromocriptine) will do nothing for HGH binding to prolactin receptors. Neither will taking supps (B6, Ldopa, etc) that support dopamine production.

If you think about it, it will make more sense.

We use Dopaminergeric drugs/supps, because dopamine directly regulates pituitary prolactin output, primarily via the D2 receptor. 
So, all these drugs/supps will lower the natural production of prolactin which is great if you have levels to be concerned about.

HGH, however, WILL STILL bind to PRL receptors even if you suppress endogenous Prolactin completely.

So, the issue is NOT prolactin per say. It is the fact that HGH BINDS to prolactin receptors additionally to naturally secreted prolactin.

No amounts of Dopamine or agonists will alter this fact.

The only positive I can see from regulating Dopamine is that it may lower endogenous prolactin significantly enough, to make up for the additional HGH/Prolactin receptor binding, thus lowering the combined additive effect of both HGH and PRL.

IMO, unless you are really sensitive to PRL, or your PRL levels are significantly raised ON TOP of large doses of HGH, I would not be so concerned with respect to HGH agonism of PRL receptors.

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## hit_my_max

Has anyone actually had this problem and reported it? How common is this? Should one consider taking Anastrozole with HGH to prevent it/be on the safe side?

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## Swifto

> Dopamine Agonists (Cabergoline, Bromocriptine) will do nothing for HGH binding to prolactin receptors. Neither will taking supps (B6, Ldopa, etc) that support dopamine production.
> 
> If you think about it, it will make more sense.
> 
> We use Dopaminergeric drugs/supps, because dopamine directly regulates pituitary prolactin output, primarily via the D2 receptor. 
> So, all these drugs/supps will lower the natural production of prolactin which is great if you have levels to be concerned about.
> 
> HGH, however, WILL STILL bind to PRL receptors even if you suppress endogenous Prolactin completely.
> 
> ...


You got any studies that state GH binds to the PRL?

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## Flex-Appeal

^ ditto
Any studies on HUMANS?...not some rat

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## Deep_Fried

> You got any studies that state GH binds to the PRL?



Yes, tons. 

This is quite common knowledge in this field. If you are interested please look into information regarding 22Kda Growth Hormone Isoform and PRL-R dimerization.

22Kda HGH is the monomer of HGH that is synthesized as the single isoform for use in pharmaceutical HGH preparations. (the EXO HGH you all use from pharma to generics is ONLY composed of 22Kda HGH)
The thing most people do not realize is that this single isoform is not the the only one our bodies produce and utilize. Our bodies produce a multitude of various isoforms and fragments as a pool of HGH isoforms containing 22Kda and 20Kda monomers, various dimers, trimers, tetramers all the way to 45Kda pentamers, not to mention numerous fragments around 5Kda.

The 22Kda (synthetic HGH) and the 20Kda isoforms both have similar structure to prolactin, which is in effect a "cousin" to HGH as they belong to the same superclass of cytokines.

22KDa (synthetic HGH) has a much greater binding affinity than 20Kda and other various HGH isoforms that would notmally be produced endogenously via the pituitary rather than the single 22Kda isoform delivered exogenously.

This is interesting and likely accounts for many of the noted side effects that people experience on HGH therapy. As we tip the balance in the body towards an unnatural ratio of 22Kda vs other isoforms, we also increase the propensity for increased Prolactin receptor agonism which curiously is responsible for more than the straight forward lactogenic effects we are most familiar with on mammary tissue.

The diabetogenic effect of HGH and proposed impact on systems affecting water retention (RRAS, ENaC) may be mediated at least partially via an increased affinity for the Prolactin receptor.

For instance with regards to HGH side effects re: hyperinsulinemia..
22Kda HGH enhances Pancreatic Beta Cell proliferation and insulin secretion which is surprisingly mediated via agonism of local Beta Cell Prolactin receptors (PRL-r), NOT via HGH receptors(HGH-r). 

Anyhow, I digress with my interest, which is probably quite boring for many.

Here are some study snippets highliting the answers to your original quetion  :Wink: 






> Cells treated with human growth hormone (hGH), which binds and activates the hPRL receptor, exhibited bell-shaped dose-response growth curves consistent with the sequential dimerization mechanism proposed for the hPRL receptor (Fuh, G., Colosi, P., Wood, W.I., and Wells, J.A. (1993) J. Biol. Chem. 268, 5376-5381).






> Prolactin (PRL) and GH have two distinct binding sites (site 1 with high affinity; site 2 with low affinity) that each interact with a PRL receptor (PRLR) to form a functional receptor dimer that activates signal transduction. (Langenheim JF, Tan D, Walker AM, Chen WY Department of Biological Sciences, Clemson University, Clemson, SC 29634-0326, USA.
> Mol. Endocrinol. 2006)






> The fourth helix (helix 4) in the human growth hormone (hGH) molecule plays a role in binding to the GH receptor as well as the PRL receptor through topologically different amino acids. (Kato Y, Maruyama O, Chung HO, Tomizawa K, Kato T Biosignal Research Center, Gunma University, Japan.Biochem. Biophys. Res. Commun. (1996)






> Previously we have demonstrated that 20-kDa human GH (20K-hGH) is a full agonist for hGH receptor (hGHR) even though its complex formation with hGHR and hGH-binding protein differs from that of 22-kDa human GH (22K-hGH). In this study, we focused on the effect of 20K-hGH on human PRL receptor (hPRLR) (Tsunekawa B, Wada M, Ikeda M, Uchida H, Naito N, Honjo M Life Sciences Laboratory, Performance Materials R&D Center, Mitsui Chemicals, Inc., Chiba, Japan. Endocrinology (1999)

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## Deep_Fried

> ^ ditto
> Any studies on HUMANS?...not some rat


The studies have always been out there. What surprises me is that many people just sit on these forums wanting "proof" of this and "proof" of that (bah humbug attitudes, lol) handed to them rather than taking an interest and initiative to search for the information they obviously seem curious about. 
Seriously, you only need a few key words from the subject matter discussed so far to come up with hundreds of articles, studies, and general research info. You are all empowered to find this info, that is the wonderful thing about the internet these days. Don't take my word on it, go see it with your own eyes and mind.  :Wink: 


Like I said, what I am stating is not some "new" information up for debate. This is established medical fact, regardless of anyones skepticism and has been known for quite some time.

BTW, the topic is regarding hGH (Human Growth Hormone ) and hPRL-R (Human Prolactin receptor)

The "H" in both signifies "human" in case there is any doubt.  :Smilie:

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## Slide

If you have had gyno surgery and the gland is removed then you would not have any tissue for this to effect correct? I know the gland is never totally removed so could GH cause what is left to grow back?

thanks deep-friend your information has been great.

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