Common Anti-Androgens can promote AR activity via ARA55

[LinuxCavalier]

Well this might not be the best news. Its already well known that antiandrogens have weird effects in people with hormone-refractory prostate cancer.

AR-associated protein 55 (ARA55), one of the AR coregulators, has been characterized as having the capacity to modulate AR specificity in response to agonists and antagonists (15). This AR coactivator has been reported to enhance AR transcriptional activity in response not only to normally weak adrenal androgens but also to the antiandrogens hydroxyflutamide (HF) and other nonandrogenic steroids, including 17?-estradiol (E2) (16–18). A frequently occurring AR mutation (mtART877A) in prostate cancer patients promotes hypersensitivity to ARA55 in the up-regulation of androgen-regulated genes. The commonly used antiandrogens, including HF, E2, cyproterone acetate, and bicalutamide, promote (instead of block) AR transcriptional activity in the presence of ARA55 in prostate cancer cells (18).

http://www.pubmedcentral.nih.gov/articl ... tid=154309

The molecular basis of androgenetic alopecia (Androgenetic Alopecia) involves two pathogenic steps. The first step
determines the androgen sensitivity of dermal papilla cells. For this 5 -reductase, androgen receptor (AR)
and AR cofactors are important. We identified an AR coactivator ARA55/Hic-5 as androgen sensitivity
regulator in dermal papilla cells. The second step determines whether androgen regulates hair growth
positively or negatively. In this step our recent data suggests that cell-specific activation of TGF- 1
promoter by androgen plays a key role.

http://iid2008.org/meetings/sshr-abs.pdf


The first article linked, does go on to show that something they call dominant-negative ARA55 mutant (dARA55) inhibits androgen receptor activity as well as the agonist effect of these antiandrogens.