Altrenogest is a commonly used progestogen for the suppression of oestrus and associated distracting behaviours that interfere with training and performance of female racehorses. The steroid is derived from 19‐nor testosterone and is structurally similar to the anabolic androgenic steroid, trenbolone. In this study, the relative androgen potency of altrenogest was determined by a kidney (HEK293) cell androgen bioassay. The HEK293 bioassay shows that in its pure form, altrenogest has a high relative potency compared with testosterone but is not as strong as β‐trenbolone. Our results also show that altrenogest is able to activate the androgen receptor at the concentrations relevant to the administration regime of racehorses and retains its activity ex vivo. Thus, we show unequivocally that altrenogest, a progestogen used widely in female racehorses, acts as a strong androgen in a mammalian cell bioassay.
Androgens, both steroidal and nonsteroidal in nature, are among the most commonly misused substances in competitive sports. Their recognized anabolic and performance enhancing effects through short-and long-term physiological adaptations make them popular. Androgens exist as natural steroids, or are chemically synthesized as anabolic androgenic steroids (AAS) or selective androgen receptor modulators (SARMs). In order to effectively detect misuse of androgens, targeted strategies are used. These targeted strategies rely heavily on mass spectrometry, and detection requires prior knowledge of the targeted structure and its metabolites. Although exquisitely sensitive, such approaches may fail to detect novel structures that are developed and marketed. A nontargeted approach to androgen detection involves the use of cell-based in vitro bioassays. Both yeast and mammalian cell androgen bioassays demonstrate a clear ability to detect AAS and SARMS, and if paired with high resolution mass spectrometry can putatively identify novel structures. In vitro cell bioassays are successfully used to characterize designer molecules and to detect exogenous androgens in biological samples. It is important to continue to develop new and effective detection approaches to prevent misuse of designer androgens, and in vitro bioassays represent a potential solution to nontargeted detection strategies.androgen, in vitro bioassay, nontargeted detection | INTRODUCTIONAndrogens have been used as performance-enhancing drugs for many decades. 1 Since their first detection in various sporting arenas, 1 a battle has ensued between the ability to detect versus evasion of detection strategies. Currently, detection relies on methods that depend on up-to-date cataloguing of all known androgens, as well as in some cases understanding their metabolism, so that reference material of parent compounds and/or their metabolites can be synthesized. The large number of known target compounds, coupled with an increasing list of emerging targets, lends itself to a nontargeted detection approach. In vitro cell-based androgen bioassays that detect on biological activity rather than chemical identification represent a feasible solution for the nontargeted screening of sports doping samples. | ANDROGENSAccording to World Anti-Doping Agency statistics for human athletes, the most abused performance-enhancing drugs are anabolic (muscle-building) agents inclusive of androgenic molecules (2019 anti-doping testing figures, WADA, www-ama.org). Reports on adverse analytical findings show that anabolic agents are responsible
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