Possibility of CJC-1295 Pituitary Enlargement

[Bobaslaw]

Hey.

I was thinking about this as I was reading a study on GHRH Knockout Mice and CJC-1295.

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse -- Alba et al. 291 (6): E1290 -- AJP - Endocrinology and Metabolism

Basically, GHRHKO mice have the inability to produce GHRH, so their pituitary glands have a smaller number of somatotroph cells. Thus they are hypopituitary.
Supplemetation with CJC-1295 and following pituitary biopsy shows and increase in the pituitary size do to increased proliferation of somatotrophs.
My question here is regarding long term use of CJC on "normal" pituitaries and whether this can lead to an enlarged pituitary down the line. It seems plausable that an overstimulation of the pituitary by supranormal GHRH levels could cause this. An enlarged pituitary can cause all sorts of issues not just related to intercranial pressure.
Any help or feedback on this would be welcome as these are pure speculations on my part and I have no concrete info other than my thoughts and the study above.

Take Care.

 

[CryingEmo]

Wow, this is scary.

 

[SOLARUS]

hmmm...someone who is hypopituitary will logically have an atrophied gland, and stimulation of it would logically increase the size, but it's another matter to say that overstimulation would make someone hyperpituitary. there may be a regulating mechanism present in "normal" glands that doesnt let them grow beyond X size, etc....i dunno.

if what you are proposing is true, then (bear with me here) supplementation of an aromatase inhibitor would logically cause your hypothalamus to grow, as it is being forcibly, but not artifically compelled to kick out more LH/FSH. obviously HCG wouldnt do that because it is effectively downstream of this feedback loop...although HCG could cause enlargement of the testes..which i think it does, to a point, and i think that's been documented...however the desensitization of the leydig cells to large doses of HCG appears to be a logical regulating factor in the testes growth. a similar mechanism of desensitization may apply for the pituitary. this scenario has been demonstrated for HCG in real-world applications, though i'm not sure it's been shown in a lab...it honestly wouldnt be all that hard to show a desensitized pituitary in a study....but didnt we see somewhere that GHRH continues to cause high GH for weeks? i wonder if the decrease happens later, if at all....

again, all speculation....

 

[SOLARUS]

...it honestly wouldnt be all that hard to show a desensitized pituitary in a study....but didnt we see somewhere that GHRH continues to cause high GH for weeks? i wonder if the decrease happens later, if at all....

again, all speculation....

here's a related study...

http://www.ncbi.nlm.nih.gov/pubmed/10474131?ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

i have my thoughts on it, but i'm curious what you other guys think and dont want to cloud your interpretations...

 

[Bobaslaw]

hmmm...someone who is hypopituitary will logically have an atrophied gland, and stimulation of it would logically increase the size, but it's another matter to say that overstimulation would make someone hyperpituitary. there may be a regulating mechanism present in "normal" glands that doesnt let them grow beyond X size, etc....i dunno.

if what you are proposing is true, then (bear with me here) supplementation of an aromatase inhibitor would logically cause your hypothalamus to grow, as it is being forcibly, but not artifically compelled to kick out more LH/FSH. obviously HCG wouldnt do that because it is effectively downstream of this feedback loop...although HCG could cause enlargement of the testes..which i think it does, to a point, and i think that's been documented...however the desensitization of the leydig cells to large doses of HCG appears to be a logical regulating factor in the testes growth. a similar mechanism of desensitization may apply for the pituitary. this scenario has been demonstrated for HCG in real-world applications, though i'm not sure it's been shown in a lab...it honestly wouldnt be all that hard to show a desensitized pituitary in a study....but didnt we see somewhere that GHRH continues to cause high GH for weeks? i wonder if the decrease happens later, if at all....

again, all speculation....

Very good thoughts, Sol.

I was also churning on whether there would be mechanisms involved in keeping a health population of pituitaty somatotrophs at a constant level even with overstimulation of GHRH. Sure there is a great difference between the growth potential of atophied tissues and normal tissues as we know.
The question is, what will happen in the long term with CJC? Will there be desensetization? How much? After how long? Will this be following any possible enlargement of the pituitary?
I'm not certain about your AI parallel, although I see the comparison. The thing with CJC is that if you run it for GH purposes, you are going to want to run it for quite a while, just as GH. How long do we really expose yourselves to an AI other than for a comparatively short PCT? Plus how much higher will levels get in that scenario compared to the large amounts of CJC(GHRH) our pituitary is seeing in the long run?
The HCG/testes comparison is one that I was actually churning on, thinking to myself, how much larger than "normal" would my testes get on HCG if they were not atrophied from a cycle? I can live with overly enlarged testes even for a short time. I don't know if I hold the same to be true to my pituitary.

Once again, great feedback.

Thanks a bunch!

Take Care.

 

[SOLARUS]

Very good thoughts, Sol.

I was also churning on whether there would be mechanisms involved in keeping a health population of pituitaty somatotrophs at a constant level even with overstimulation of GHRH. Sure there is a great difference between the growth potential of atophied tissues and normal tissues as we know.
The question is, what will happen in the long term with CJC? Will there be desensetization? How much? After how long? Will this be following any possible enlargement of the pituitary?
I'm not certain about your AI parallel, although I see the comparison. The thing with CJC is that if you run it for GH purposes, you are going to want to run it for quite a while, just as GH. How long do we really expose yourselves to an AI other than for a comparatively short PCT? Plus how much higher will levels get in that scenario compared to the large amounts of CJC(GHRH) our pituitary is seeing in the long run?
The HCG/testes comparison is one that I was actually churning on, thinking to myself, how much larger than "normal" would my testes get on HCG if they were not atrophied from a cycle? I can live with overly enlarged testes even for a short time. I don't know if I hold the same to be true to my pituitary.

unfortunately if someone is really worried about pituitary growth, they have to take the "safe route" and adminster GH! (yknow, as opposed to CJC/GHRH)...likewise if we wanted to preserve our hypothalamus, we need to inject T instead of using an AI! okay, maybe that's saying too much

as for long-term versus short-term...i personally dont want to use CJC for long periods - i only want it for steroid cycles, when i can use it best for real growth. afterwards, i dont care, but then again i am still young....this attitude may change with time.

i see the allure of a long-term CJC protocol, but honestly i see problems: one of the following 2 cases will (logically) play out:

1) the pituitary will desensitize and the stuff will stop working very well...OR
2) your pituitary will enlarge because it is constantly being compelled to release GH....

what we really need is a more complete picture of how this system works...can you (a person with a normal pituitary)actually increase the number of somatotrophs, or do you just keep the ones you have very busy producing GH? is there a potential to run out of raw materials for GH? any other dimensions we need to consider? what other feedback loops are there?

i find it hard to believe that a given somatotroph will just produce GH at very high levels for very long....and honestly, if it does, it should be given time to recover....which lends itself to a cycled CJC protocol preference...whereas GH you could run ED for years and not worry too much, except about your checking account.

 

[Bobaslaw]

here's a related study...

http://www.ncbi.nlm.nih.gov/pubmed/10474131?ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

i have my thoughts on it, but i'm curious what you other guys think and dont want to cloud your interpretations...

Seems like hex eventually desensitized its ability to promote a response for further administrations, yet this did not affect the response when GHRH was introduced instead... Both seem to be targeting different receptors (subtypes?).

 

[pumbertot]

I guess we may never know the answer to this guys. There does indeed have to be some risk of pituitary enlargement with longer term use of CJC, although I believe its a small risk.

I prefer to be safe and run CJC in between peptide cycles to re-establish good GH levels, such as post rHGH usage when the pituitary gland output is lower.

Was just thinking that surely if pituitary enlargement is possible with long term overtsimulation of the gland by CJC, then shrinkage would also be possible with long term usage of rHGH?

 

[Bobaslaw]

I guess we may never know the answer to this guys. There does indeed have to be some risk of pituitary enlargement with longer term use of CJC, although I believe its a small risk.

I prefer to be safe and run CJC in between peptide cycles to re-establish good GH levels, such as post rHGH usage when the pituitary gland output is lower.

Was just thinking that surely if pituitary enlargement is possible with long term overtsimulation of the gland by CJC, then shrinkage would also be possible with long term usage of rHGH?

I agree pumber! Cycling CJC is the most responsible approach, as with most everyhting else we do here.

I see your point about pit shrinkage from GHRH suppression due to exogenous GH. Makes sense just like any other organ with secretory cells. (Testicle shrinkage from exogenous Test)

 

[pumbertot]

worth a read and does seem to indicate that GHRH may cause pituitary hyperplasia.


http://www.hormones.gr/pdf/Pituitary_hyperplasia.pdf

Growth hormone releasing hormone (GHRH) can cause somatotroph proliferation leading to hyperplasia 2,22,28-30

but take note of the opening remarks

The hyperplasia could be physiologic which is usually reversible, or pathologic which varies in presentation from incidental to tumor like lesion with and without hormonal disturbance. Any pituitary cell is capable of undergoing hyperplasia in the presence of the right stimuli.

which would suggest to us that if hyperplasia does take place, it may reverse when the stimulus is removed.

 

[Bobaslaw]

worth a read and does seem to indicate that GHRH may cause pituitary hyperplasia.


http://www.hormones.gr/pdf/Pituitary_hyperplasia.pdf

Great read! I'm in the middle of it right now, thanks a bunch.

This along with the KO mice study definitely shows the reality. It just makes sense, as we see this kind of behavior in all other interdependant hormonal organ processes causing a hyper or hypo state. (Thyroid enlargment from long term high TSH output, Testicular increase/atrophy due to high or low LH output, etc)

but take note of the opening remarks which would suggest to us that if hyperplasia does take place, it may reverse when the stimulus is removed.

Yes, I agree. Same can be seen with leydig cell hyperplasia/atrophy due to increased LH and Drop in LH output.

Well, back to reading the doc.

Take Care.

 

[kesam]

With this in mind what do you feel would be the optimal cycle lengths for CJC.

Many thanks