This is quite interesting. This study states that antagonists can act as agonists depending on ligand binding affinity, concentration, and the presence of competing natural ligands. Take a look…
What I find even more interesting is that cyproterone acetate, an anti androgen, can promote dna binding…
Please take a look at this study. Thanks
jbc.org/content/270/34/19998.full
Abstract
The mechanism of antiandrogenic activity of vinclozolin (3-(3,5-dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione), a dicarboximide fungicide under investigation for its potential adverse effects on human male reproduction, was investigated using recombinant human androgen receptor (AR).
The two primary metabolites of vinclozolin in plants and mammals are M1 (2-[[3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid) and M2 (3′,5′-dichloro-2-hydroxy-2-methylbut-3-enanilide). Both metabolites, in a dose-dependent manner, target AR to the nucleus and inhibit androgen-induced transactivation mediated by the mouse mammary tumor virus promoter. M2 is a 50-fold more potent inhibitor than M1 and only 2-fold less than hydroxyflutamide. In the presence of dihydrotestosterone (50 nM), M2 (0.2-10 μM) inhibits androgen-induced AR binding to androgen response element DNA. In the absence of dihydrotestosterone, concentrations of 10 μM M2 or hydroxyflutamide promote AR binding to androgen response element DNA and activation of transcription. Agonist activities of M2 and hydroxyflutamide occur at 10-fold lower concentrations with the mutant AR (Thr to Ala) endogenous to LNCaP human prostate cancer cells. The results indicate that androgen antagonists can act as agonists, depending on ligand binding affinity, concentration, and the presence of competing natural ligands.
Introduction
The human androgen receptor (AR) 1 is a member of the steroid hormone receptor family of ligand-activated transcriptional regulatory proteins required for normal male sex development. Androgens through their receptor stimulate masculinization of the fetus and induce male imprinting of the developing brain. Molecular defects in the AR gene cause the syndrome of androgen insensitivity, which results from failure of AR androgen binding, nuclear import, DNA binding, and/or transcriptional activation(,1). Certain antiandrogens, such as hydroxyflutamide, [i]bind AR with moderate affinity, promote nuclear import/i, but inhibit androgen-mediated transcriptional activity by failing to promote DNA binding, whereas others, such as [Size=4]cyproterone acetate[/size], [Size=4]promote DNA binding at moderate concentrations and induce partial agonist activity.[/size]