The Di Loreto study showed very similar findings as Baylor (1.36 fold vs 1.4 fold increase).
https://www.researchgate.net/profile/Carla-Di-Loreto/publication/263355013/figure/fig2/AS:341840252424211@1458512475657/Comparison-of-demographics-features-immunohistochemical-findings-and-serum-hormonal.png
As you can see it differs quite a lot between tissues though. AR density in stromal cells had roughly a 1.7 fold increase. Where epithelial “only” had 1.23 fold change, while vessel smooth muscle AR actually was slightly underexpressed (although not statistically significant).
When they end with this though it really makes one wonder. If the overexpressed theory is true, wouldn’t more AR mean more problems?
- “Our unexpected observation that percentage of AR positive stromal cells is inversely related to ASEX score, suggests that patients less able to raise AR are those with more severe side effects related to sexual dysfunction.”
I’d really want some studies looking into the local DHT levels and check the ratio to AR. If there is indeed normal DHT and still overexpressed AR we can scrap that theory for good.
This is a great read about CRPC, they show how AR is negatively regulated by androgens etc.
- Liganded AR negatively regulates its own expression by binding to a site in the second intron of the AR gene, and this repression is relieved by AR-targeted therapy.
I fully support Axo’s new research, but I still feel that checking local DHT as a intermediate step would have been a good idea.
Also since the Baylor study showed 2000+ dysregulated genes, something more than the AR has to be involved in my opinion. AR don’t modulate that many genes (from what I understand), but it might be domino effect (or due to some other pathways fin blocked).