|HOME SCHEDULE AUTHOR INDEX SUBJECT INDEX|
PH01 Endocrine Disruption
(PH008) In vivo Confirmation of the Anti-Androgenic Nature of Flutamide in the Fathead Minnow.
Jensen, K1, Defoe, D1, Makynen, E1, Kahl, M1, Linnum, A1, Ankley, G, 1 U.S. Environmental Protection Agency, Duluth, MN, USA
ABSTRACT- A short-term reproduction assay with the fathead minnow (Pimephales promelas) 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 (AR) in the fish. The goal of this study was to determine whether flutamide exerts effects through blocking activation of the AR in reproductively-mature female fathead minnows. Adult female fathead minnows were exposed to the androgen -trenbolone (water concentration, 500 ng/l) for two weeks in the presence and absence of flutamide (400 g/l). 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 (production of nuptial tubercles, structures normally only present in mature males). 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. This abstract does not necessarily reflect EPA policy.
Key words: anti-androgen, fathead minnow, endocrine disruption, mechanism of action
Internet Services provided by|
Allen Press, Inc. | 810 E. 10th St. | Lawrence, Kansas 66044 USA
e-mail firstname.lastname@example.org | Web www.allenpress.com
All content is Copyright © 2003 SETAC