Endocrine Abstracts

Chemical-analytical methods are currently in use as the gold standard approach for the detection of androgens, designer androgens and selective androgen receptor modulators (SARMs) in serum and urine samples from athletes as well as in sports supplements. These methods are exquisitely sensitive and selective. However, they have the disadvantage in that the androgens that being surveyed for must have delineated structures. Designer androgens or SARMs that have divergent structures from the characterized reference list can be missed with analyte methods because their specific analytical fingerprints are not defined. In vitro cell based androgen receptor (AR) bioassays are based on probing the biological pathway of androgen action and therefore are capable of identifying the presence of any AR-activating compound in a sample. Moreover, by basing the AR bioassays in different host cells (eg. yeast- no metabolism or cofactors; HEK293- limited metabolism but has cofactors; HuH7- active metabolism and cofactors) the relative AR potency of activating compounds can be measured. Using this tandem AR bioassay approach, 15 SARMs, recently detected as sports doping agents, were analyzed for relative AR potency. For S-1, S-6, S-23, S-24, ostarine, andarine, LG-121071, Rad-140, LGD-2226, 93746 and BMS-564929 all showed only moderate intrinsic AR bioactivity in the yeast bioassay, however potency increased dramatically with active metabolism. Some of these SARMs showed AR potencies far beyond that measured for the endogenous androgens, testosterone or dihydrotestosterone. AC262536 and MK0773 were weak SARMs even after active metabolism. By contrast, ACP-105 and YK-11 were both potent SARMs, with and without metabolism. Together, these results have implications for the anabolic potential of these SARMs, thus they pose a real threat to sports doping.