Igf-1/tamoxifen

Marc-Antony

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Tamoxifen interferes with the insulin-like growth factor I receptor (IGF-IR) signaling pathway in breast cancer cells.Guvakova MA, Surmacz E.
Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

The insulin-like growth factor I receptor (IGF-IR) is involved in the control of breast cancer cell growth. The cytostatic activity of tamoxifen (Tam), a nonsteroidal antiestrogen, is partially mediated through interference with IGF-I-R-dependent proliferation, yet the effects of Tam on IGF-IR intracellular signaling have never been elucidated. Consequently, we investigated how Tam modifies the IGF-IR signaling pathway in estrogen receptor-positive MCF-7 breast cancer cells and in MCF-7-derived clones overexpressing either the IGF-IR (MCF-7/IGF-IR cells) or its major substrate, IRS-1 (MCF-7/IRS-1 cells). MCF-7/IGF-IR and MCF-7/IRS-1 cells exhibit greatly reduced estrogen growth requirements but retain estrogen receptors and express sensitivity to antiestrogens comparable to that in the parental cells. In all tested cell lines, regardless of the amplification of IGF signaling, a 4-day treatment with 10 nM Tam produced a similar cytostatic effect. In MCF-7 and MCF-7/IGF-IR cells, growth inhibition by Tam was associated with the reduced tyrosine phosphorylation of the IGF-IR in the presence of IGF-I; however, the basal level of the IGF-IR remained unaffected. Moreover, Tam inhibited both basal and IGF-I-induced tyrosine phosphorylation of IRS-1, which was accompanied by down-regulation of IRS-1-associated phosphatidylinositol 3'-kinase activity and reduced IRS-1/growth factor receptor-bound protein 2 (GRB2) binding. In contrast, under the same treatment, tyrosine phosphorylation of Src-homology/collagen proteins (SHC; another substrate of the IGF-IR) and SHC/GRB2 binding were elevated. The protein levels of the IGF-IR and IRS-1 were not modified by Tam, whereas SHC protein expression was either not affected or moderately decreased by the treatment. In summary, this work provides the first evidence that in MCF-7 cells, cytostatic effects of Tam are associated with the modulation of IGF-IR signaling, specifically with: (a) down-regulation of IGF-I-induced tyrosine phosphorylation of the IGF-IR; (b) inhibition of IRS-1/phosphatidylinositol 3'-kinase signaling; and © up-regulation of SHC tyrosine phosphorylation and increased SHC/GRB2 binding. It is hypothesized that dephosphorylation of IRS-1 could be a major contributing factor in Tam cytostatic activity.



So this article raised my curiousity ... tamoxifen interferes with Igf-1 R in breast cancer cells. So that's good news against gyno.

But now does it make sens to say that Tamoxifen could interfere with igf-1R not only in breast tissue ... and that in this case running igf-1 on cycle or during PCT is not the best idea. I know the affinity for oestrogenic tissue is very high for tamoxifen, and I doubt that tamoxifen will bind to muscular igf-1R, but could it slightly effect your igf-1 cycle. Making it ideal to run it OFF cycle.

Let me know what you guys think.
 

Tom 185

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bump. no replies to this?

i'm in my 2nd week of clomid/igf and switching to tamoxifen next week..
 

PumpingIron

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Someone might be able to correct me if I'm wrong, but there is a difference between IGF-IR and IGF-1.
 

PumpingIron

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So this study is saying tamoxifen citrate down regulates that receptor?
 

Marc-Antony

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So this study is saying tamoxifen citrate down regulates that receptor?
Tamoxifen interferes with the insulin-like growth factor I receptor ... in breast cancer cells ... not down regulated ... but Tamoxifen binds to igf-1R. Like sand in a slot.

The question is to what extent can we assume that tamoxifen could bind to other types of tissue (muscle IGF-1R ...) or is the binding of Tamoxifen just too specific (to oestrogenic tissue) ...
 
thesinner

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So (in theory) IGF and tamoxifen could be synergystic, in that, it would allow for more IGF-1 to go to IGF-1R's in muscle tissue?
 

Marc-Antony

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So (in theory) IGF and tamoxifen could be synergystic, in that, it would allow for more IGF-1 to go to IGF-1R's in muscle tissue?
If I understand what you are saying ...

We could imagine that IGF-1 R is occupied by Tamoxifen in breat tissue (read gyno) ... and that the igf-1 not being associated to igf-1R in breast tissue could find it's way to igf-1R in muscle cells.

But, I don't think, it's gonna work like that ... 'cause for one oestrogenic IGF-1R in men is very low (after all no man wants a pair of boobs), and for two I would say that tamoxifen binds mostly to oestrogenic tissue, or else we could treat prostate cancer with it.

So I don't know. I'd say Tamoxifen shouldn't interfere with muscular IGF-1R ... but in that case I can't see how taking tamoxifen (post cycle therapy) is gonna cause a decrease in IGF-1 by ~20% (posted by yourself).

How does tamoxifen interfere with igf-1 production.

Cause it's either IGF-1R is downregulated or desensitized ... or Tamoxifen interferes with igf-1 production in the liver (due to it's hepatotoxicity ????), or directly on hgh, in that case everybody should stop using Tamoxifen and go on Clomid, or some other serm.

If you can answer this question this should really help all of us understand this better. What are/is the binding site(s) of Tamoxifen? If it's solely IGF-1R in breast tissue (makes sens, cancer cells won't spread/grow anymore) ... then I don't see how Tamoxifen could negatively interfere on IGF-1 levels, and in that case, if someone were to experience gyno, I could see how in some cynical way it could be good for muscular growth ... more igf-1 binds to igf-1R in muscles.

Hope this makes sens.
 
TripDog

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interesting thread....subscribed
 

Marc-Antony

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Here is what I am thinking ... short version, but that's what I've come to think.

First, I was kinda, igf-1 during post cycle therapy ... I don't know ... doesn't sound like the best idea. My main concern ... hepatotoxic coumpounds in general, coming from an oral, or using Tamoxifen or some other hepatotoxic serm. Igf-1 being produced by the liver ...

Then I thought, what about, "shutting down igf-1 production" by the liver ... easily done, let's just run igf-1 during post cycle therapy. Liver is already going through such a hard time with hepatotoxic coumpounds ... allowing mister liver to stop igf-1 production might do him some good. (like training on an injury, not the smartest move).

So first, I was like with serm's, AI's, test boosters, liver protectant, cardiac support, and all .. why add even more igf-1. But, now, I am thinking hey why not.

Then I thought to myself, apparently, from what I've read results from igf-1 during PCT aren't that great compared to igf-1 alone cycles ... it's hard to be sure if that's really the case or not ... And, I think that the reason is probbaly because all those compounds may be interfering with igf-1 ... or maybe hepatotoxic compounds have weakend the liver, which in return is producing less igf-1 ...

Bottom line, it might in fact be a better idea to run igf-1 during PCT, than on its own ... but it looks to me like doses have to be readjusted for PCT. Clearly, injecting 1mcg/2.2lbs/1kg is gonna give better results during PCT ... when you can easily have good gains just following a 40-60 mcg protocol IM bilat, postworkout.

Now, there is to more things to concider:
1/ going on a split injection protocol ... although igf-1 has a longer half life than slin ... I don't think it will exceed 8-10 hours ... so 2-3 injections day may very well be a better protocol than postworkout only, as you may have read a few times already now .. I think Palumbo's protocol is about that, not sure right now. But he swears by 5-10 mcg's injections ... I don't think it will do the trick that well, especially on a short cycle.

2/ tappering down ... I haven't read much about it ... but come to think of ... tappering down might be a good idea ... although endogenous producton of IGF-1 recovers very fast post igf-1 cycle. ha ... those supposed somatotropin boosters might come in handy after all now that you think about it. PCT for igf-1 with one of those hgh boosters. :D
 
jonesboy

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No expert here. but from what i have read on other threads tomax inhibits igf production. why not just use some ralox instead. Plus igf can cause prolactin gyno as it did with me. so a good serm like ralox which is better for prolonged use would be the better alternative..

gh/igf/pmgf all seem to give me gyno.. just a heads up...
 

Marc-Antony

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gh/igf/pmgf all seem to give me gyno.. just a heads up...
True that ... Something to think about too. From my understanding of serms .... Tamoxifen would be your best pick to avoid gyno, don't know how well rolaxifen compares to Tamoxifen for growth factor induced gyno.

Looking at the article posted above ... Tamoxifen looks just about right, high affinity for IGF-1R in breast tissue.
 

chainsaw

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I am planning on running IGF-1LR3 in my PCT but I will be using Toremifene, will be okay to run these together.
 
thesinner

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I am planning on running IGF-1LR3 in my post cycle therapy but I will be using Toremifene, will be okay to run these together.
Should be plenty fine, toremifene is tons less toxic than Nolvadex. Good Luck with your PCT :thumbsup:
 

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