Androgen-and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays

作者：Keiler Annekathrin Martina; Zierau Oliver; Wolf Sylvi; Diel Patrick; Schaenzer Wilhelm; Vollmer Gunter; Machalz David; Wolber Gerhard; Parr Maria Kristina

来源：Toxicology Letters, 2018, 292: 39-45.

DOI：10.1016/j.toxlet.2018.04.026

• Saccharomyces cerevisiae
• Formestane
• 4-Hydroxytestosterone
• Doping
• Molecular modeling

4-Hydroxyandrost-4-ene-3,17-dione, also named formestane, is an irreversible aromatase inhibitor and therapeutically used as anti-breast cancer medication in post-menopausal women. Currently, no therapeutical indication led to approval of its 17-hydroxylated analog 4-hydroxytestosterone, an anabolic steroid. However, it is currently investigated in a clinical trial for breast cancer. In context with sports doping, aromatase inhibitors are administered to reduce estrogenic side effects of misused anabolic substances or their metabolites. Therefore, both substances are prohibited in sports by the World Anti-Doping Agency (WADA). Analysis of urinary phase I and phase II metabolites showed similar results for both compounds. In the current investigation, 4-hydroxyandrost-4-ene-3,17-dione, 4-hydroxytestosterone and seven of their described urinary metabolites as well as 2 alpha-hydroxyandrostenedione were tested in the yeast androgen screen and the yeast estrogen screen. Androgenic effects were observed for all tested substances, except for one, which showed anti-androgenic properties. With regard to the yeast estrogen screen, estrogenic effects were observed for only two metabolites at rather high concentrations, while six out of the ten substances tested showed anti-estrogenic properties. In terms of the strong androgenic effect observed for 4-hydroxytestosterone (10(-8) M), 4-hydroxyandrost-4-ene-3,17-dione (10(-8) M) and two more urinary metabolites, the yeast androgen assay may also be used to trace abuse in urine samples.

• 出版日期2018-8