"If 5ar were damaged, supplementing DHT should have a massive positive effect. "
Awor, I sincerely appreciate your efforts on raising awareness regarding AR receptor downregulation. So please don’t take this the wrong way - you b need to consider that BOTH mechanisms are at work here[/b]. Some evidence that both are involved are subjective, but consider the following:
1.) JN had medium term success supplementing with Human Growth Hormone (GH), and I have had some success using arginine based GH secretagogue (symptoms decreased espcially erectile, and IGF-1 doubled). Why is this significant? Because GH acts to upregulate androgen sensitivity. AND higher IGF-1 levels boost 5AR2 activity (higher GH triggers higher IGF-1). I have bloodwork to prove this, although it is not a pure experiment, as I raised total serum T by ~ 100% using low dose clomiphene, and at the end of an 8 week cycle of secretagogue, with both effects combined my Adiol-G was raised around 50% (still subnormal even by Quests wide open range, but up nonetheless along with symptom relief). Yes increased serum T means greater substrate for 5AR2 to react upon. If I get a chance I will test Adiol G again with T adjusted up a little over 100% from baseline, but no secretagogue, to seperate out the secretagogue effect from the increased substrate effect.
2.) Have been reading, on and off, a book on androgen receptors, prepared by one of the top world experts in the field… Funny thing here - an entire chapter is devoted to discussing 5AR2. And sections of 2 or 3 other chapters also discuss 5AR2 at some length. If AR and Adiol-G (5AR2 activity marker/metabolite) are completely unrelated then why would a world renowned AR expert include this information?
3.) Have been studying, since I got my first piss poor adiol-G serum level back, all the food and food substances that inhibit 5AR2. Amazing, the AR book has a Chapter 6 that talks about foods that downregulate AR. Ready for this? Green tea polyphenols, quercetin, Resveratrol, DHA, all downregulate AR in the prostate (resveratol lowers levels of AR related proteins in all areas). And all these substances are ALSO 5AR2 inhibitors.
4.) The 5AR2 gene SRD5A2, the AR receptor genes, and the vitamin D receptor gene VDR are all part of the same superfamily. While not yet grasping the entire significance of this, consider that just about every single member of this forum, that has had vitamin D tested, turns out to be deficient, and, even for those that have supplemented with very high doses, remain somewhat deficient. Please refer to the vitamin D thread and my comments in a couple places there. It would appear that the connection here is more than casual . . .
I totally agree with you that the AR receptor theory is hard to grasp, even for those of us that have a scientific background. The mechanics of 5AR2->Adiol-G and finasteride effects are much easier for all of us to begin to understand. Please keep an open mind, and BTW, if you happen to know how the androgen receptor interacts with inhibin I am all ears. And your quote above - oversimplifies in that what appears to be important is where we make DHT, not just how much we have of it. If we aren’t converting it in the prostate, pituatary, and testis via 5AR2, the normal DHT levels resulting from 5AR1 activity in the skin may not in fact result in much progesterone to allopregnanolone conversion. .Does AR downregulation effect allopregnanolone (or other neurotransmitter) synthesis? If not how to explain those on this forum with brain fog?
The future may in fact prove that AR downregulation is causative to 5AR2 suppresion. If and when that is proven I will owe you a beer or three. In the mean time I find that both theories overlap and support one another, more than compete with one another. Sorry if my tone sounds harsh, do not intend for it to be. And yes, I’ve been remiss in posting some of my own results.
Respectfully - kazman