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IN VIVO CONFIRMATION OF THE ANTI-ANDROGENIC NATURE OF FLUTAMIDE IN THE FATHEAD MINNOW
Citation:
Jensen, K M., D L. DeFoe, E A. Makynen, M D. Kahl, A. L. Linnum, AND G T. Ankley. IN VIVO CONFIRMATION OF THE ANTI-ANDROGENIC NATURE OF FLUTAMIDE IN THE FATHEAD MINNOW. Presented at SETAC Annual Meeting, Austin, TX, November 9-13, 2003.
Description:
A short-term reproduction assay with the fathead minnow has been developed to detect chemicals with the potential to disrupt reproductive endocrine function controlled by estrogen- and androgen-mediated pathways. As part of characterizing the assay, tests have been conducted with a variety of chemicals with known mechanisms of action in better-characterized mammalian models. For example, previous work has shown that the mammalian anti-androgens vinclozolin and flutamide both affect reproductive endocrinology of female fathead minnows in a relatively similar fashion. However, the nature of the responses to these chemicals is general enough that it is difficult to ascertain whether or not they are actually mediated through antagonism of the androgen receptor in the fish. The goal of this study was to determine whether flutamide exerts effects through blocking activation of the AR in reproductively-mature fathead minnows. Adult female fathead minnows were exposed to the androgen B-trenbolone for two weeks in the presence and absence of flutamide. Previous studies with trenbolone in our lab have shown that the androgen binds with high affinity to the fathead minnow AR in vitro and displays androgenic activity in vivo, as indicated by masculinization of the females. Co-administration of the flutamide with the trenbolone completely blocked masculinization of the fish, thus providing direct in vivo evidence that flutamide exerts effects as an AR antagonist in the fish.