Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin andto the bovine progestin receptor

For the steroidal growth promoters trenbolone acetate (TBA) and melengestro l acetate (MGA) neither the complete spectrum of biological activities nor the potential endocrine disrupting activity of their excreted metabolites i n the environment is fully understood. The potency of these substances in [ H-3]-dihydrotestosterone ([H-3]-DHT) displacement from the recombinant huma n androgen receptor (rhAR) and from human sex-hormone binding globulin (hSH BG) was evaluated. In addition, the potency for [H-3]-ORG2058 displacement from the bovine uterine progestin receptor (bPR) was tested. For comparison , different anabolics and synthetic hormones were also tested for their bin ding affinities. For 17 beta -trenbolone (17 beta -TbOH), the active compou nd after TBA administration, an affinity the rhAR similar to dihydrotestost erone (DHT) and a slightly higher affinity to the bPR than progesterone wer e demonstrated. The affinity of the two major metabolites, 17 alpha -trenbo lone and trendione, was reduced to less than 5% of the 17 beta -TbOH-value. The affinity of these three compounds and of MGA to the hSHBG was much low er compared with DHT. MGA showed a 5.3-fold higher affinity than progestero ne to the bPR but only a weak affinity to the rhAR. The major MGA metabolit es have an affinity to the bPR between 85% and 28% of the affinity of proge sterone. In consequence, MGA and TBA metabolites may be hormonally active s ubstances, which will be present in edible tissues and in manure. We conclu de that detailed investigations on biodegradation, distribution and bio-eff icacy of these substances are necessary.