+ 5 Dominant receptor binding
IrishMack brought up in an earlier post that Trens dominant receptor binding is actually bro science due to the fact there has been zero human testing done with tren. I had heard this for so long from so many that I thought it was a proven fact & the only question remaining was what happened with the unbinded test if tren was dominant. The fact that no human testing has been done does not mean it’s not true, it just means there’s no scientific proof. I tried to research recent testing to see what the findings were. I couldn’t find any. I’m interested in knowing if anyone else has any pertinent information or is this all spectacle upon individual experience? Does anyone know of studies to back this up in animals? If you have an opinion, post it & let’s see what we comes up with. Keep it mature :-))
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This thread is gold! Going right in the favorites list. Thanks guys
Yes sir ;)
Ive fead as much as i can stomach on this topic in endo lit and books. Some of it is very accessible but a lot is not. There is also a lot they seem to admit is hypothesised and/or currently unknown.
But, a lot is known...
This is at nuclear/molecular level, so even imaging this in your mind is tough. Any given cell will have tens of thousands of receptors and only 5% approx might need to be activated to elicit a physiological response. There are several factors involved in that including binding of the ligand to the receptor (1 factor). Also involved is binding affinity, number of receptors, volume of ligand, tissue selectivity, activation of co-regulators and more.
Binding affinity means the amount of ligand needed to activate 50% of receptors on a cell, the higher the affinity the less amount of tren for example is needed. In cells whose receptor molecules and in contact with ligand molecules from competing ligands, the one witth thr higher affinity will 'win' where the volume is similar/same/greater. This happens with dht over testo in the prostate, showing even despite a fraction of the volume total compared to test, the greater collecrion and 10x binding affinity of dht to Androgen receptor it wins every time. Interesting.
5a reductase which converts testo to dht seems to have a compounding effect on T to increase its binding affinity but this does not happen in skeletal muscle which is devoid of 5aR. This explains why nandrolone exerts greater effect than test in muscle
Its also important to mote that even if we wanted to get into a discussion about ratios based on the above... we cant really... at any basic level... because as the compounds move through the various parts of the body they meet different enzymes which metabokise thr compounds. Again using DHT as thr example, there is an enzyme in muscle that reduces dht, so even if there is a negligible bit of dht on the skeletal muscle any possible effect will be negligible if any effect on the AR at all. Something of note is that in environmental studies (how bovine treated meat/dung/water puts tren into our ecosystem) of Tren was shown a significant ability of tren or tren metabolites to remain stable through the ecosystem and retaining its ability to elicit effects as it moves to a different food chain. (Test breaks down easier than tren, basically).
There are some very complicated maths that go towards calculating the ability of 1 ligand to bind over another, and i am not a maths guys but if anyone wants to look at it, its in the refs below. Its possible to do this but there are a lot of variables. Still, even though the measurements and maths are complicated, Bauer and his pals have a very easy to comprehend presentation on how much (or how little) it takes in ligand concentration to outcompete other ligands with lower (or higher) binding affinities.
The lit makes it very clear that although we cannot talk in absolutes (a single receptor is bound, all receptors are bound, none are bound etc blah blah - even the pro's dont know all of it, hell molecules werent even microscoped intil last year or the year before iirc!) the 19-nors will out compete testosterone in skeletal muscle a hell of a lot, if not most of the time depending on variables. This leaves test to be metabolised elsewhere. That said it is dose dependant, but there are other factors too (i cant find the link but read some lit that mentioned tren may inhibit test at the ligand binding site... if i find it i will post a follow up).
As i said before, the proof is in the eating of the pudding. Ive experimented with this using deca, and the results are blatantly, blatantly obvious. Anyone who says or thinks otherwise has not read up on this yet and could not have purposely tested it which brings us right back to the beginning comments on broscience.... which all of this is including my basic lit review!
I had to download a lot of this including books so you might need to search it out of interested in reading or i could prob email anyone who wants something specific by email, a pdf or whatever.
On a side note... i came across, in several publications, discussion on how different hormones exert influence on receptors we might think they dont... like test exerts on estro receptors to a small extent. This could feed many discussions including how gh can influence prolactin estrogen and thibgs like gyno... maybe
Also there is a process well documented where peptide hormones elicit local growth in target tissues they are released from. Anyone interested in whether gh injections can cause local growth should read up on this for their answer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439524/
BOLAND, molecular biology, 3rd edition
https://www.ncbi.nlm.nih.gov/books/NBK20/#!po=55.1948
https://www.researchgate.net/publication/19139429_Comparison_of_the_rece...
Biomolecular Ligand-Receptor Binding Studies: Theory, Practice, and Analysis. Charles R. Sanders, Dept. of Biochemistry, Vanderbilt University
European Commission opinion of the Review of previous SCVPH opinions of 30 April 1999 and 3 May 2000 on the potential risks to human health from hormone residues in bovine meat and meat products, 2002
Characterisation of the affinity of Merent anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor - E. R. S. BAUER et al
Thanks mate for all you’ve added here. I knew you’d come in with opinion & some reference, & that’s why I started this thread .... for a good conversation & learning experience
Its such an interesting topic
Well done for getting it going. Im looking forwsrd to others bringing more info. The more we learn the better for all of us
Once again you bring it brother!Good job.+
Its still wide open for discussion though because i firmly include melysef in the group who dont fully understand it all lol
The gas thing is, the most recent publications i went over... consistently admit how little is really known and how new hypotheses have merit for things like where the receptor is actually located. Its mind blowing. Then when you visualise a cell, how small it is... and imagine there are 50k androgen receptors on it.... and all it takes is 5% of them to be bound to activate protein systhesis or dna rna reactions.... and then cnsder the size of a tren molecule... and.... holy kaw.... it really is mind blowing
Wow!! It’s truly mind blowing man.... thanks pal
Trens binding affinty is about 2 to 3 times stronger than test, and has about 5 times the activity of test at the receptor level, but some test gets converted to dht which has an even stronger affinity then tren to androgen receptor.
Receptor affinity changes in different tissue types, dht being more active in prostate tissue than skeletal muscle
Binding affinities of most androgens
Receptor affinity doesn't equal receptor activation
http://2.bp.blogspot.com/-EZPBo-MiUFk/TlJlBB_QZ9I/AAAAAAAAB4I/HZhW8EyC7n...
That’s a cool chart & very informative... I wonder how they came to this conclusion.... was it through human studies I wonder? Thanks brother +1
I wonder about where they got the info. Nandrolone has a 22% affinity to the prog receptor and shows none on this chart.
I was wondering the same thing man! I found the original post & article
http://suppversity.blogspot.com/search?q=Receptor+binding
I agree with Mack. Think about it, one can run test deca dbol etc and everything's all good, but run test and tren and the tren is not going to allow the test to bind to receptors? How does that even make the least bit of sense logically? Anyone know how many receptors there are throughout the body lol. A ton, more then enough for alll the test and tren you can inject to bind. Don't think anyone can run enough gear for a compound to cover all the receptors in the body.
On another note. A little different but same principle. Take opiates for example, one takes something like heroin, overdoses, they administer nalaxone (narcan), it has such a strong affinity for the receptor it displaces all the heroin and what was the receptors is replaced by nalaxone. While the nalaxone is active it doesn't matter how much of a full agonist one takes, it's not gonna do shit. Now this is a case of an agonist vs antagonist. While test and tren are both agonists. Idk, gotta be a lot of mu delta and kappa receptors in the body and the dose of narcan saturates all of them. Maybe there is a saturation dosing point with tren. But again narcan is an antagonist specifically designed to do what I just stated. Two full agonists like oxycoodone and heroin will work together. Test and tren are both agonists so based off they should both work together.
Rusty is right in terms of proving the point yourself.
Id say that if we can accept the actions of an antagonist we can probably accept that some steroids can compete harder. This is afterall what our pct's are partly based on.... one molecule can block another but even still i dont think we should think in absolutes, that is to say; we shouldnt assume that tren blocks all test or doesnt block any, if you know what i mean.
I'll see if i can dig up some endo books today... the mechanism of action is what we need to understand and how to properly explain binding affinity versus competition. Its clear we havent had a molecular biologist chime in yet!!
RustyhookerTake opiates for example, one takes something like heroin, overdoses, they administer nalaxone (narcan), it has such a strong affinity for the receptor it displaces all the heroin
You answered your own question.....thats called binding affinity. Which is why trens rated 5x as strong.
Working together? Of course they can work together. But common sense is when test isnt used, its left to do nothing but convert. Or.... lack of bibding affinity.
Whats funny to me is if we compared anything on here but tren, its all ok and simple. Use the tren work and common sense flew out the window.
Whats stronger in binding? Winny or anavar?
https://en.m.wikipedia.org/wiki/Trenbolone
Wiki sucks but the citations can be cross checked with medical citations. Just the beginning of research
100% bang on target on all accounts!
Thanks brother! Appreciate all you’ve added my friend!
Amen brother. This is everything I wanted to say plus some. Especially about the amount of receptors.
And you know what makes even more receptors? Test... also tren... also deca... this list goes on.
Area-1255As far as I know its a very high-affinity androgen receptor agonist, with particularly central effects (brain binding).
mindblown! this is why eroids is awesome
Id respectfully disagree with that opinion. The pharmacos of tren were documented/translated in the 70s. You might find it difficult to translate dosages when moving across different creatures but not how the binding etc. works. The main receptors operate more or less the same across vertibrate animals/humans. You see it a lot (big dosage differences) with rat studies. Less so with doses used in bovine studies.
What is known is that 19-nors have a higher binding affinity for the AR. What is also known is that progestins have a blocking effect on testo at the AR, 19-NOrs being mild progestins. Doesnt take a lot to hypothesise from there.
To test it in a sense... use tren to suppress testo and see what happens to estro. Then add testo and see what happens to estro. Hint: Tren doesnt significantly aromatise.
I've done this with deca which does actually aromatise but at a far lower rate than testo. The results are blatantly obvious. But you could measure it if you really did want to test it.
I respectfully disagree with that, the physiology and chemistry of an animal versus a human is completely different, the closest they found was chimps and pigs and off base is rats and they certainly havent injected tren into either one.
Like I said in that post, the only way to tell which one works for every different individual is trying out both ways. I dont do tren because I dont think the side effects are worth losing a few pounds or gaining 2 pounds of muscle, a hardened diet will do exactly the same. Does tren take over the receptors? Well if it really does how come some people can run high test and low tren and blow the fuck up and others try the same and all they do is sweat and have bad sides? Then the other guy who is low test high tren has no sides and also very little gains? I see it all the time here and also the pics. Do we blame the ugl? Not when you read the si and one guy swears he gained 10 pounds of muscle and looks as veiny as a prick and someone else looks like it was his first time lifting a weight. What happened? 2 different people, different genetics, different training and eating habits. Which goes to say there is no right or wrong way to do a tren cycle, its experimenting to see what works for the individual.
Idk Irish wouldn't say completely different. There are probably more similarities between mammals physiology vs differences, depending of course. Like the great apes genetic structure and chromosomes are the closest we have to humans. Mice a little more different, and so on. But the Androgen receptor is remarkably similar in its amino acid profile. And binding affinity to the same drug (of course not proven unless compared side by side multiple times) I imagine would also be similar. This is just on a molecular level of course. Everything else you mention like individuals genetics (possible gene mutation, etc), training, nutrition, is going to change the game as well.
Well of course we have different physiology to fish etc! But in terms of the sex steroids/receptors, how they work is based on what type of receptprs they are. The numbers of types can differ though, eg. Fish might have more estro receptors than humans. But how they work when bound... activation transcription expression, protein synthesis etc. Its the same process as far as i see in everything ive read.
I agree with sides completely. Its the same with all medications really but as far as i am aware those sides are due to any given individuals enzyme levels in their body. So lets say, for example, I have a load of fat and you are hella lean... i possibly have a hell of a lot more aromatase than you which can translate as a bigger conversion rate of test to estrogen which means i will experience worse sides than you such as water retention, high BP, messed up electrolyte levels and all of that good stuff
Experimenting... couldnt agree more with you
Rustyhooker^^^^^
RustyhookerWell its called broscience simply because only tren hex was used on humans with lil recorded info.
The testing on animals though shows how they came up with 500/500. It wasnt pulled out someones butt. Its binding affinity as collected in specimins. During clinical experiments.
Broscience shows as we use it theres less sides. How many folks need ai or have da use with low test? Why do ya think the old farts here advice low test on the first tren run? If it was just fake bs then why not just run 500/500 ? Ever see that openly advised? Definitly not. If its broscience then why do we advise tren a first? Do we advise npp before deca?
Personally, my first tren a run was 30mg prop with 75mg tren a being found as my comfort zone. Sweating, hunger gone and lack of cardio was my only sides.
In another post, Flash & I briefly discussed how some pain meds wasn’t as effective while using Tren. I’m wondering if it’s due to the tren or the estrogen binding capabilities? Estrogen I know plays a part in the effects of pain.... Is the estrogen binding to the receptors blocking the compounds from the meds being able to bind?
I don't have alot of experience with tren but I do have a lot with DHB which I would consider to be a receptor hog. When I run a cycle I usually use Adex .25mg E3D for estro control if using around 500mg of test. Now if I run a cycle of like 400mg test e and 400mg DHB I have to bump up my adex to .25 EOD to keep estro under control. I can run 500mg of test with EQ or primo or pretty much every other compound (tren excluded) here and only need my .25mg of Adex E3D but through in a receptor hog like DHB and boom my estro goes up and I need more AI to combat it.
I guess I am going on broscience from my experience here, but DHB is touted to have a high receptor binding affinity. This seems to be the case when I use it. It is preferentially binding to the receptors leaving the test with no where to go but to aromatize. Based off the experience I have had is why I would recommend lower test with these high binding affinity compounds like DHB and tren. Broscience at its finest but it is all we really have to work with.
Would it not be better to just lower the amount of test in the first place,or is there an advantage to keeping the test high?
I personally don't see much of an advantage running test high in that situation. To me it seems like I am taking more compounds than my body can handle or effectively use. That is why when I run those compounds now I basically just run a trt dose of test and let the other compounds do the heavy hitting for. I think you may also be able to get away with bumping up those compounds to take advantage of them with your test dose being lower now.
I also just feel so much better when I run my test at trt doses and don't have to worry about taking any ai. Most of my cycles lately have just included trt doses. Maybe the ai's drag me down but I have so much more energy and focus when I don't have to use them. Heck, my best cycle ever was when I eliminated test for a large chunk of the cycle. I would just dose the test based upon how it makes you feel during a cycle. If you need high test with tren to feel good then do it but don't be afraid to run low doses of test either. You may feel a whole lot better running it that way, just need to find out what works for you. I think people are often times afraid of running test on the low end thinking they will not get as good of gains, which is not true. You will have plenty of other androgens doing work and sometimes test just gets in the way.
This is EXACTLY my train of thought. I used to run test high all the time...600mg aweek min. I aleays thought thats what you needed to do to run a successful cycle. Now 300 aw of test is ALOT for me....lol. A couple years back i was running 500mg of test a week with some EQ at 900mg. At the end of the cycle i added 525mg of trenA a week. About 10 days into the cycle i felt like complete dogshit. I have run this tren dose many times in the past with no issues. I went and got bloods and sure as shit my estro was at like 150...lol. I never changed my AI when adding the tren, only added 1mg of caber a week like i always do. I couldn't figure out why i would need more ai on the say amount of test i was using for months. Then it dawned on me......the tren was binding more then the test and leaving all that test just floating around to convert. Im not daying that is the gospel truth to why this happened but it sure made sense, especially after i dropped my test to 200mg and my estro dropped too.
Now i almost always run my test at 200mg. Lets be honest anyway....test sucks...lol. I use enough to keep me normal and let the rest of the stack do the work.
That answered my question perfectly.I always believed the bro science of going 1/1 ratio at least or even test 2/1.I'm changing my mind on that the more I read and more higher level guys I talk with.An acquaintance of mine just got his pro card and he never runs test above TRT.He also almost never runs AI.He is in the same school of thought as you with let the more anabolic compounds do their work.
I'm on Tren right now (wk 12) and haven't added in an ai because my test is at 315mg pw. I obviously keep it on hand of course to be safe but I haven't needed it and nor do I ever when I keep my Test low.
My next bulk cycle in early spring will be with 250mg of test pw
Don’t be afraid to try it bro. You can always up the test if needed. I will note that some people have to run the test closer to equal or a little higher to combat sides such as depression etc.... it’s not true for everyone, but it’s something to be aware of especially for those prone to depression & such. Depression can & will have a great affect on the body in many ways & can be a big hindrance to gains & a successful cycle.
My line of thinking is lower sides from less estro.I don't use deca but I do use bold cyp and tren.Both are receptor hogs,so maybe the sides i was getting is actually from the test,rather than the others.
Thanks again my friend for your input! So by experience you can see your e2 levels rise if your test is very high when cycling a receptor hog? I am thinking that this is the reason it’s repeated as gospel due to experiencing the higher e2 levels. I don’t believe it was just a theory someone thought up & started preaching. This would be actual evidence in a sort. Is this true in everyone I wonder or is it different on an individual basis?
If I don't lower my test I have to up my AI if running DHB compared to if I was running test and another compound. I have only used low dosed test with tren so I haven't been able to test that theory with tren. It is somewhat of an individual thing I suppose, but if you look at the comments of the majority of the people who run tren, there seems to be a pattern that most prefer to run it with lower test. I think this has a lot to do with tren's superior binding affinity leaving the test floating around and causing problems if it is ran too high.
In my limited experience I love the first few weeks of tren then its like a switch goes off and it turns into a nightmare. I ran 50 tren, 100 prop EOD on top of my 200 cyp trt per week. I’ve run caber or prami for prolactin and adex for estrogen
Yeah some people just have those negative sides. I have a friend that went 3 weeks & won’t ever touch it again.
I love it like no other compound but it turns me into someone else.Feel like super man act like bizaro!