SHBG questions

[English]

OK, that's interesting. I am a bit confused now by the rules governing the sensitivity of AR's. After reading a study on rat penile tissue, which revealed that the higher the presence of DHT the more up-regulation of the AR occurred (which was opposite to the hypothosis the author was trying to prove!) I was under the impression that all receptors would up-regulate/sensitise is the presence of more of the androgen the particular AR is programmed to take- even though even to me this does seem counter intuitive.
If i recall correctly, CDSNUTS recovery by cycling pro hormones was based on this theory - though that was just one facet of his programme so no one can ever know whether that element was critical or not.
I'm open to using clomid in the future, but i just need to know for sure why i am doing something. Your explanation makes sense if it is correct for sure that the E receptor becomes more sensitive in the absence of E - this is certainly logical, but how do you know that? Is there a study or whatever demonstrating this?

What you are saying does also make logical sense when applied to a finasteride users issues. They take fin, their T rises (due to DHT being blocked), users often feel great for a while (i certainly did) then E rises. Meanwhile the AR's downregulate in the presence of additional T and E, causing ever more E to be produced (based on a desensitised Pituitary/hypothalmic E receptor action + no DHT present to reduce E), leading to very high SHBG and ultimate crash.

Almost all Fin users get high E symptoms at some point - Personally, i grew an enlarged left nipple! So it is fairly safe to say high E is the beginning of the issue.

So i do believe you are right, but like i say, i would love to know of any studies on this as i can only find the rat one which demonstrates the exact opposite (i appreciate rats aren't human!)

Finally, onto the long term use of AI resulting in low T and E - yeah i have read the results of the year long trials of an AI which resulted in T starting to fall around month 6 and continuing to do so until month 12 in all users. To be fair though end T levels were still at around 17 with a baseline of around 10/11 ish, so they were still way higher. This is why i think i can buck that trend:

1- I have noted that most AI users only need the higher doses for a short while - 8 weeks or so, then they can cut the dose to a fraction and maintain healthy E levels, which i plan to do.
2- The moment i have energy, i workout. The trials used obese and hypogonadal patients who were in that position for - most probably - reasons of diet and exercise, so it is no wonder their bodies couldn't persistently kick out higher T.
3- If you are correct regards the E receptor upregulating in the presence of less E, then i should be able wean off completely before the long term trend of lowering T kicks in - ie within a year.

I am looking for your comments on whether this all makes sense by the way! I am dangerous at the moment as i have a little knowledge!

If you tell me my plan makes sense, i will go for it for the next 12 months, and if i am still not where i need to be, then i will use clomid, provided you can point to some evidence that E receptors sensitise in the absence of E etc.

I really appreciate your help Jel. Having a plan is only any good for me when i both believe in it and understand why i am doing it, hence your explanations are very helpful.

[entropy]

That isn't actually strictly correct. DHT upregulated 5ar activity, I have the studies around here somewhere.

[Jelisej]

Your plan does make sense to me, with AI's receptors sensitivity should increase as well.

Most of the time down regulation happens when hormone levels are high- purpose is decreasing the number or affinity of receptors to reduce sensitivity of target tissue when hormone levels are chronically elevated.

And when hormone levels are low body responds in increasing the number or affinity of receptors so that tissue will still respond even if the hormone level is depressed .

But sometimes some hormones can upregulate its receptors as well- if I remeber correctly Growth hormone upregulates its receptors, not sure for DHT


And there is an interesting theory, called "receptor control theory"-
the receptor control theory postulates that our set points for regulating weight, energy, or pleasure are variable; they are directly related to the number, sensitivity and location of cellular receptors in our bodies, and can be modified by changing the number and sensitivity of these receptors.

[tallstraw]

Yeah GH does im pretty sure does. The longer you're on it the better it does for you. I've read that before too.

Actually I take it back. I think it's that it just doesn't down regulate...there's no suppression or change to your own natural production. So you get double benefits.

[nate3993]

Yeah GH does im pretty sure does. The longer you're on it the better it does for you. I've read that before too.

Actually I take it back. I think it's that it just doesn't down regulate...there's no suppression or change to your own natural production. So you get double benefits.

no, it'll make ur body not produce it anymore just like taking test stops your balls from making it.....it's jus to a much lower degree then steroids and your body can bounce back much quicker.

this I'm pretty sure of. feel free to correct if I'm wrong

[entropy]

OK, that's interesting. I am a bit confused now by the rules governing the sensitivity of AR's. After reading a study on rat penile tissue, which revealed that the higher the presence of DHT the more up-regulation of the AR occurred (which was opposite to the hypothosis the author was trying to prove!) I was under the impression that all receptors would up-regulate/sensitise is the presence of more of the androgen the particular AR is programmed to take- even though even to me this does seem counter intuitive.
If i recall correctly, CDSNUTS recovery by cycling pro hormones was based on this theory - though that was just one facet of his programme so no one can ever know whether that element was critical or not.
I'm open to using clomid in the future, but i just need to know for sure why i am doing something. Your explanation makes sense if it is correct for sure that the E receptor becomes more sensitive in the absence of E - this is certainly logical, but how do you know that? Is there a study or whatever demonstrating this?

What you are saying does also make logical sense when applied to a finasteride users issues. They take fin, their T rises (due to DHT being blocked), users often feel great for a while (i certainly did) then E rises. Meanwhile the AR's downregulate in the presence of additional T and E, causing ever more E to be produced (based on a desensitised Pituitary/hypothalmic E receptor action + no DHT present to reduce E), leading to very high SHBG and ultimate crash.

Almost all Fin users get high E symptoms at some point - Personally, i grew an enlarged left nipple! So it is fairly safe to say high E is the beginning of the issue.

So i do believe you are right, but like i say, i would love to know of any studies on this as i can only find the rat one which demonstrates the exact opposite (i appreciate rats aren't human!)

Finally, onto the long term use of AI resulting in low T and E - yeah i have read the results of the year long trials of an AI which resulted in T starting to fall around month 6 and continuing to do so until month 12 in all users. To be fair though end T levels were still at around 17 with a baseline of around 10/11 ish, so they were still way higher. This is why i think i can buck that trend:

1- I have noted that most AI users only need the higher doses for a short while - 8 weeks or so, then they can cut the dose to a fraction and maintain healthy E levels, which i plan to do.
2- The moment i have energy, i workout. The trials used obese and hypogonadal patients who were in that position for - most probably - reasons of diet and exercise, so it is no wonder their bodies couldn't persistently kick out higher T.
3- If you are correct regards the E receptor upregulating in the presence of less E, then i should be able wean off completely before the long term trend of lowering T kicks in - ie within a year.

I am looking for your comments on whether this all makes sense by the way! I am dangerous at the moment as i have a little knowledge!

If you tell me my plan makes sense, i will go for it for the next 12 months, and if i am still not where i need to be, then i will use clomid, provided you can point to some evidence that E receptors sensitise in the absence of E etc.

I really appreciate your help Jel. Having a plan is only any good for me when i both believe in it and understand why i am doing it, hence your explanations are very helpful.

So by that logic, suppression of dht via reductase would increase receptor concentration even though dht isn't the problem? Thus cessation of finasteride or other reductase inhibitors would restore the concentration of dht to normal except there's a tonne more receptors than needed? What kinda issues do you think that could cause, Jel?

[English]

I see what your getting at Entropy, logically - on finasteride, the absence of DHT and free T (given high E and SHBG concentrations) - receptors would have upregulated based on Jels comments. Upon cessation of the drug, the body is flooded with DHT and with heightened receptor sensitivity this would lead to the massive high and return of function which PFS guys speak of, which lasts just a day or 2, then they crash, which you would think would be the receptors burning out in some way.
Jel mentioned that GH can help upregulate receptors. That is good to hear because when i was tested my IGF/1 came back slightly high (just out of range) I guess that could explain why i am doing better than most maybe.

Would exercise, in particular HIIT and heavy weights + decent diet help increase receptor sensitivity? As recovery stories tend to include these things.

I get my bloods back today and will post later.

[English]

Oh and thanks entropy for clarifying that rat study, which does make more sense. Nice to not have that muddying the waters.

[English]

I have bloods back after being on AI for a month:
Testosterone: 27.9 Range (8-28) was 20
Free Test: 79 (35 to 90) was previously low in range
Estrogen: <18 (ie undetectable but could be anything under 18) Range (20 -50) This was 36 last time
SHBG: 35 (18 to 55) This was 51 so it is falling nicely
LH: 4.2
FSH: 3.6

So above looks good with exception to E, which i obviously need to raise to slightly above 18 (in order to get it detected) I don't think i have completely crushed E as i am functioning fine still, however i do think i am too low as i had a raging thirst that i could not get rid of for days.
Here's my plan and also my observations. I am writing these things to illicit comment in order to check i am on the correct path:

My observations on these results:
1- They confirm my HPTA is intact and working
2- SHBG must have been previously raised because of high E2 and low free androgen given it is now falling (as per Jels comments)
3- E is too low and needs to be detectable (as close to 20 as poss)

My plan
1- concerning SHBG, it is important i think for it to keep falling before i start raising E by much at all. I have noted it can take months for the final settled SHBG figure after free T is raised and E brought down. If i allow E to rise again too much now, then i will not have enough free T again if total T goes down a bit and SHBG rises a bit (which they almost certainly will), so i need to keep SHBG going down for a while until it gives me a buffer
2- So i plan to lower the AI dose from 1mg a day to 0.5mg EOD (hopefully this will be enough to keep E about the same or maybe slightly higher, but not lower it any more)
3- Re-test in a month.

[Jelisej]

So by that logic, suppression of dht via reductase would increase receptor concentration even though dht isn't the problem? Thus cessation of finasteride or other reductase inhibitors would restore the concentration of dht to normal except there's a tonne more receptors than needed? What kinda issues do you think that could cause, Jel?

Increased number of receptors should not pose problem, they would decrease over time.