Oestrogenic and (anti)androgenic activity of zearalenone and its metabolites in twoin vitro yeast bioassays

Selected resorcylic acid lactones (RALs) – zearalenone (ZEA), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) were investigated for their oestrogenic and (anti)androgenic activity using twoin vitro RIKILT yeast Estrogen and Androgen bioAssays. Our results show that all tested compounds are able to induce hERα-dependent transcription and the rank of their potencies, based on EC50 values is as follows: α-ZOL > α-ZAL > ZEA > β-ZAL > β-ZOL. None of the tested compounds appeared to be androgenic when tested individually at concentrations ranging from 0.1 pM to 0.1 mM. However, all RALs inhibited 17β-testosterone-induced transcriptional activity. The highest antiandrogenic potential showed α-ZOL, β-ZAL and β-ZOL with the IC50 of 6.2 μM, 11.5 μM and 15.2 μM, respectively. When compared with flutamide, for which a relative antiandrogenic potency (RAAP) was assumed as 100%, the corresponding RAAPs for α-ZOL, β-ZAL and β-ZOL were 220, 119 and 89.8%, respectively. In summary, our study revealed that RALs possess not only oestrogenic, but also antiandrogenic activity. Further research is warranted to clarify the role of disruption of androgen receptor signalling in humans and animals.