Receptor Downregulation

General Discussion
#1

Further to Mariobros post:

I dont know if this is correct but, wouldnt LH and FSH levels tell us whether or not there is in fact an androgen receptor problem? So if these two values continued to rise while TRT was given to the patient that would indicate that the body doesnt sense there is testosterone in the system right?

But this is not the case with Finasteride guys is it? Dont their LH and FSH drop with when TRT is given?

Am I on the right track here in arguing that this may purely be an estrogen problem?

Please chime in guys, this has got me curious.

#2

What is Mariobros post? Provide link pls.

#3

I was just saying that if there was a problem with androgen receptor insensitivity, perhaps SARMS (Selective Androgen Receptor Modulators) could be useful. I haven’t done a lot of extensive research into this, just thought i’d put it out there.

I guess the basic reasoning why i thought androgen receptor insensitivity could be a problem was that post fin men who go on TRT often don’t feel the beneficial effects, e.g. Awor.

J89, as i understand it LH and FSH release from the pituitary are controlled by GnRH release from the hypothalmus, which is regulated by the feedback loop of estrogen.

So if we injected ourselves with testosterone, our bodies would convert some to estrogen through aromatose, as presumably our aromatose is fine, and then this would react negatively on the hypothalamus, resulting in decreased GnRH, and thus decreased LH and FSH.

So i guess that yeah excess estrogen is definitely a problem for a lot of guys here, but is it as simple as lowering estrogen? i don’t know… i’m probably over my head at this point haha.

I can speculate on what happens to the remaining testosterone that is not converted through aromatose but this is difficult. In an ordinary person some would be converted to DHT via 5ar1 and 2 and some would go to the receptor sites and activate the beneficial effects of testosterone (muscle growth etc). Some post fin guys have very high blood DHT, some low. Some guys are hypogonadic, some have good testosterone levels but still feel like shit.

Adiol G seems be consistently low amongst those that have tested it so a lot of us are looking at low or inactive 5ar2 as a source of the problem and i believe this theory makes sense personally as inhibiting 5ar2 is the core function of finasteride.

I guess if the androgen receptors are fine then i can’t really think of a reason why a protocol like JN’s would not work, as long as estrogen is monitored and controlled which the Masteron should help to do as DHT is suppressive of estrogen i understand. He is basically switching his HPTA from autopilot to manual control.

#4

I did not know this. I thought it was regulated by Androgens…

#5

You might be right, it might be only in women that GnRH is controlled by estrogen. I haven’t researched it in detail.

Ok, did a quick google:

hptaxis.com/technology/hpta/

In males, luteinizing hormone (LH) secretion by the pituitary positively stimulates testicular testosterone (T) production. The pulsatile secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates LH secretion. Regulation of the secretion of GnRH and LH is by the negative feedback of testosterone and estradiol at the level of the hypothalamo-pituitary. Estradiol has a much larger, inhibitory effect than testosterone, being 200-fold more effective in suppressing LH secretion. 5a-reduction, DHT, does not appear to play a significant role in the negative feedback effect.

Estrogens contribute substantially to the negative feedback regulation of gonadotropin secretion. A great part, if not all, of the inhibitory effect on gonadotropin secretion is mediated by the endogenous conversion of testosterone to estradiol. The restraining action of estrogens on gonadotropin secretion in men is exerted both at the pituitary and at the hypothalamic levels.

So it seems that both testosterone and estradiol effect the HPTA, however excess estradiol would appear to cause greater suppression of LH.

#6

So why then, with people who had dignosed defective androgen receptors, have raised LH both before and after TRT?

#7

Um i’m not sure i think i need to read abit more into this before i comment any further, again i’m not really an expert on this stuff.

I was actually re-thinking my earlier post. Even if estrogen is 200 more suppressive on the HPTA than testosterone, under normal circumstances men have only a very small amount of estrogen and high testosterone levels so it’s likely that testosterone is the major factor in the HPTA feedback loop in men.

#8

Did anyone happen to email the contact on HPT axis? not sure if taht company is open anymore…, but the email is mscally@asih.net

#9

Funny thing noone ever mentions that dht is more than 10x potent than testosterone and lots of guys in here have been over the range high in dht! Why cant dht be the suppreser? Just weird that this option (a very likey one too) is never even discussed. It has to be estrogen right? cause we know now that estrogen is bad as we knew dht was bad when we took propecia…

Alot of old men have low t and lots of estrogen yet they dont have half the issues we do.

Wonder how one would feel with very high dht and low testosterone and medium estrogen. Maybe like we do… :smiley: ? Its also a combination i would think is very rare for a normal person as dht drops while ppl age. I dont think there are alot of older men with low T and loads of dht. How come this is never discussed ? its always estroen and most of us dont feel a difference when we use anti-e…

#10

Along these lines, I took fin on two separate occasions (the first time for about a year; the second time for a few years) with a couple years or so in between. I felt terrible when I stopped taking it for the first time, and did feel relatively better (both mentally and genitally, more so mentally) for a period when I started back up again. I can’t remember exactly the time line, or how much worse things were as my second stint endured, but could I have felt better due to a block of DHT? If this is happening what might be a treatment that could alleviate a downregulation of androgen receptors due to a relative excess of DHT after acute fin withdrawal (without exacerbating unwanted effects). Would it make sense to take a strong DHT or 5AR inhibitor for a short period of time and ween off over a longer duration?