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INTERACTION OF TRENBOLONE, A POTENTIAL FEEDLOT EFFLUENT CONTAMINANT, WITH HUMAN AND RAINBOW TROUT ANDROGEN RECEPTORS (AR) AND IN VIVO ANDROGENIC EFFECTS IN THE RAT
Citation:
Wilson, V S., C. R. LAMBRIGHT, J. S. OSTBY, E. M. WILSON, M. C. CARDON, P. C. HARTIG, L. J. GUILLETTE JR., AND L. E. GRAY. INTERACTION OF TRENBOLONE, A POTENTIAL FEEDLOT EFFLUENT CONTAMINANT, WITH HUMAN AND RAINBOW TROUT ANDROGEN RECEPTORS (AR) AND IN VIVO ANDROGENIC EFFECTS IN THE RAT. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Concern has arisen regarding the presence and presistence of trenbolone in the environment. Trenbolone acetate is an anabolic steroid used to promote growth in beef cattle. Trenbolone acetate is hydrolyzed to the active compound, 17b-trenbolone, which is one of the primary metabolites then excreted by cattle. Both reproductive alterations in fish living in waters receiving feed-lot effluent and in vitro androgenic activity in feedlot effluent samples have been reported . In the current study, the potency of 17b-trenbolone was examined both in vitro and in a short term in vivo screening assay for androgenic activity. In COS cell binding assays using transfection of rainbow trout or human AR, trenbolone competed equally well for [3H]R1881 binding to either AR with relative binding affinities of 4.0 % and 3.4%, respectively, versus 100% for R1881. Trenbolone was also tested for its ability to activate androgen dependent transcription at concentrations ranging from 1 pM to 10 mM in MDA-kb2 cells with endogenous human AR and a stably transfected androgen responsive luciferase reporter. Trenbolone was a full AR agonist in these cells producing a dose response curve similar to that of dihydrotestosterone. Futhermore, agonist activity was inhibited by the AR antagonist, hydroxyflutamide. Trenbolone was also a potent AR agonist in the N/C terminal interaction assay performed in HeLa cells, an assay that is highly specific for androgens. When examined in vivo in the Hershberger assay, trenbolone displayed selective AR mediated (SARM) activity, affecting some androgen-dependent tissues in rats more than others suggesting that 5 alpha reduction inactivated the parent compound. In summary, trenbolone is a potent SARM. Further studies are needed to determine whether trenbolone is present in feed-lot effluent and to characterize the ability of this chemical to alter vertebrate reproduction and development.