Novel yeast bioassay system for detection of androgenic and antiandrogenic compounds

Recently, certain environmental endocrine disrupters have shown to act as antiandrogens. This suggests that environmental antiandrogens may also be crucial contributors to the increasing incidence of male reproductive abnormalities, requesting the screening and classification of antiandrogenic chemicals. Here, we report the development of a rapid, simple and effective yeast detection system for androgenic and antiandrogenic compounds, which is based on the yeast two-hybrid protein interaction. A yeast strain, ARhLBD-ASC1, was established by co-transformation of yeast cells harboring a lacZ reporter plasmid with two vectors expressing each of LexA fused hinge-ligand binding domain (hLBD) of androgen receptor (AR) and B42 fused ASC-1 that interacts with the AR-hLBD in an androgen-dependent manner. In this yeast strain, androgens, but not other hormones, strongly stimulated the beta-galactosidase activity in a dose-dependent manner. The AR antagonists flutamide, cyproterone acetate and spironolactone, and environmental antiandrogens p,p'-DDE and vinclozolin all inhibited the response of the yeast cells to 10 nM testosterone, qualitatively similar to their inhibition reported in mammalian cell systems. Furthermore, the bioassay can be performed with the simple X-gal staining on microtiter plates, suggesting this system as a powerful tool for practical and efficient screening of environmental compounds for their androgenic and antiandrogenic activities.