new guy--been on TRT for 1 year (blood test results)

[pfuked]

actually it is 2 binding sites per dimer...since they exist in homodimers. regardless, I bet my shbg is saturated...

anyways that point about 1 binding site per shbg is irrelevant anyways...

to summarize, because the complex exists as a dimer (meaning 2 shbg are bound together, which hold a total of 2 hormones) my original comment was actually right if you assume they exist as monomers

 

[pfuked]

and free e2, if it is completely unbound isn't a fraction of total---free is the total LOL

 

[johndoesmith]

and free e2, if it is completely unbound isn't a fraction of total---free is the total LOL

Some interesting stuff you posted earlier, I'm reading into this and thank you for giving me something new to learn.

I do disagree that total doesn't include free hormones. For example, free testosterone is generally a few percent of total testosterone.

 

[pfuked]

Well, let me state it the correct way. If total e2 is unbound, free e2=total e2. Not the other way around lol.

 

[johndoesmith]

Well, let me state it the correct way. If total e2 is unbound, free e2=total e2. Not the other way around lol.

If ALL of your SHBG is bound, yes. I highly highly doubt all of your SHBG is bound, and 100% of your E2 is unbound and free floating. If you think you have about .5pg/ml of free E2 that's unbound, thus keeping you from experiencing low E2 symptoms I don't think that's correct.

If that's how it worked, then bodybuilders would never suffer from crashed E2. They have significantly higher test levels on blast than you right now, and usually lower SHBG as some intentionally lower SHBG with different compounds, but they still suffer from crashed E2.

 

[pfuked]

Here is the paper I read the other day stating shgb monomers bind a single hormone. I just cy and pasted the relevant paragraph rather than posting the whole paper, but feel free to look it up for yourself if youwant

Steroid Ligands Bind Human Sex Hormone-binding Globulin in Specific Orientations and Produce Distinct Changes in Protein Conformation
The Journal of Biological Chemistry August 30, 2002

The realization that the steroid-binding and dimerization domains of human SHBG are located within its amino-terminal laminin G-like (LG) domain (6) prompted us to crystallize this region of the molecule (7) in a complex with 5α-dihydrotestosterone (DHT). This allowed us to visualize the structure of the steroid-binding site (8) and to fully appreciate the results of earlier affinity labeling experiments (9, 10) as well as biochemical studies of recombinant human SHBG variants containing specific amino acid substitutions (11). Subsequent analysis of the amino-terminal LG domain of SHBG has revealed several other features of the molecule that add new dimensions to our understanding of its structure and function. These include a confirmation of the proposed dimer interface and the demonstration that each SHBG monomer contains a functional steroid-binding site (12) rather than a single binding site at the homodimer interface (13). Our crystal structure studies have also led to the discovery that SHBG is a zinc-binding protein and that occupancy of a zinc-binding site alters the specificity of steroid binding (14). This zinc-binding site lies within a loop region that was disordered in our original crystal structure (8): a region of particular interest because it is poorly conserved between species (15) and amino acid substitutions within it influence steroid-binding specificity (11). Resolution of the structure of this extended loop region has recently helped us to understand how zinc influences the conformation and steroid-binding specificity of human SHBG (16).

here is a link to an actual diagram of DHT binding to SHBG --take a look at figures 2 and 3 http://emboj.embopress.org/content/19/4/504.figures-only

 

[pfuked]

If ALL of your SHBG is bound, yes. I highly highly doubt all of your SHBG is bound, and 100% of your E2 is unbound and free floating. If you think you have about .5pg/ml of free E2 that's unbound, thus keeping you from experiencing low E2 symptoms I don't think that's correct.

Well I did crunch the numbers and it looks like I have approx. 1000x more testosterone molecules compared to SHBG protein (micro-molar levels versus nano-molar levels) since 1 SHBG binds 1 molecule of testosterone, and since I have an excess amount of testosterone, one would assume all of my SHBG is bound up by the excess testosterone. If this is true, than practically none of my e2 will be bound to SHBG because its all bound up by excess testosterone... Unfortunately, this scenario doesn't add up since if it did I should have way more free testosterone than what is reported in my blood test. So, hormone binding to SHBG is a little more complex than I thought. I'll look into it further..

 

[johndoesmith]

Well I did crunch the numbers and it looks like I have approx. 1000x more testosterone molecules compared to SHBG protein (micro-molar levels versus nano-molar levels) since 1 SHBG binds 1 molecule of testosterone, and since I have an excess amount of testosterone, one would assume all of my SHBG is bound up by the excess testosterone. If this is true, than practically none of my e2 will be bound to SHBG because its all bound up by excess testosterone... Unfortunately, this scenario doesn't add up since if it did I should have way more free testosterone than what is reported in my blood test. So, hormone binding to SHBG is a little more complex than I thought. I'll look into it further..

Thank you for posting that paper, seriously.

You're also leaving out DHT. DHT has a higher affinity for SHBG than testosterone does.

Plus you're forgetting about albumin in your calculations I think.

You also never responded to what I said, about steroid users still being able to crash their E2.

This is a complex topic, that I doubt is able to be calculated so simply even though I'd love to figure it out, hopefully someone more knowledgeable than I can comment maybe Dr saya?

 

[1Draw]

Extremely low estradiol with none of the symptoms? I would retest with estradiol sensitive test to make sure not a lab error. Just does not make sense at all.

 

[pfuked]

Thank you for posting that paper, seriously.

You're also leaving out DHT. DHT has a higher affinity for SHBG than testosterone does.

Plus you're forgetting about albumin in your calculations I think.

You also never responded to what I said, about steroid users still being able to crash their E2.

This is a complex topic, that I doubt is able to be calculated so simply even though I'd love to figure it out, hopefully someone more knowledgeable than I can comment maybe Dr saya?

Adding DHT into the mix will only make SHBG more saturated and unable to bind e2

I don't think albumin binds testosterone or other hormones

not sure about steroid users crashing their e2. Never heard of any cases but I haven't looked

 

[Speed]

Hmmm, I thought that DHT products like proviron block e2 receptor sensitivity or I'm wrong ?

 

[johndoesmith]

I don't think albumin binds testosterone or other hormones

Then you need to read more about hormones and how they work.

not sure about steroid users crashing their e2. Never heard of any cases but I haven't looked

Happens pretty often. Why you don't have symptoms is a mystery.

 

[pfuked]

Proviron inhibits the enzyme that converts test to e2 I think

 

[pfuked]

Then you need to read more about hormones and how they work.



Happens pretty often. Why you don't have symptoms is a mystery.

No symptoms, I'm getting big and ripped, I can get a hardon on demand, and I feel pfuking great!

 

[johndoesmith]

No symptoms, I'm getting big and ripped, I can get a hardon on demand, and I feel pfuking great!

Have you ever had E2 tested before while on this protocol? the only thing I can think of is that it's a lab error. It's hard to believe a guy feels good with crashed E2.

 

[pfuked]

Have you ever had E2 tested before while on this protocol? the only thing I can think of is that it's a lab error. It's hard to believe a guy feels good with crashed E2.

Before starting trt my e2 was 9 pg/ml so maybe normal for me is in the low range.

 

[johndoesmith]

Before starting trt my e2 was 9 pg/ml so maybe normal for me is in the low range.

Same range as the other test?

you never had these symptoms pre trt or now? http://dosagemayvary.com/high-estrogen-vs-low-estrogen-symptoms-for-men/

When my E2 was 8, I was absolutely unbearably miserable, it was just awful.

 

[Speed]

If I was you I would try now and test how I feel on only 0.25mg 2x week. And gradually decrese until full stop. If bad symptoms come back, you will be sure that you need it. And of course, do labs for every experiment.

 

[Dr Justin Saya MD]

There is a free estradiol test (rather expensive) available.

1+1 doesn't always =2 in the hormone world. Sometimes it seems as if the laws of physics don't apply (this is why there isn't a comparable "laws of physiology" or biology). SHBG binding is a complex and not completely understood phenomenon. Molar mass also has to be taken into account as well as variations in binding affinity.

At the end of the day, if one is feeling great...well then more power to you regardless of what the numbers say.

 

[johndoesmith]

There is a free estradiol test (rather expensive) available.

1+1 doesn't always =2 in the hormone world. Sometimes it seems as if the laws of physics don't apply (this is why there isn't a comparable "laws of physiology" or biology). SHBG binding is a complex and not completely understood phenomenon. Molar mass also has to be taken into account as well as variations in binding affinity.

At the end of the day, if one is feeling great...well then more power to you regardless of what the numbers say.

I stand corrected then.

Out of curiosity, do the risks not apply if the person doesn't have symptoms? As in, lack of symptoms shows enough E2 for him, so no risks of osteoporosis and su?ch