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Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model
Citation:
ANKLEY, G. T., K. M. JENSEN, M. D. KAHL, E. J. DURHAN, E. A. MAKYNEN, J. E. CAVALLIN, D. MARTINOVIC, L. C. WEHMAS, N. D. MUELLER, AND D. L. VILLENEUVE. Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 99(3):389-396, (2010).
Impact/Purpose:
The purpose is to study the antagonism of the androgen receptor which is an important mechanism through whiich the hypothalamic-pituitary-gonadal (HPG) axis of fish can be affected by environmental contaminants.
Description:
Antagonism of the androgen receptor (AR) is an environmentally-relevant mechanism through which the hypothalamic-pituitary-gonadal (HPG) axis of fish can be affected. However, there are few in vivo tests specific for the detection of chemicals that act as AR antagonists. In this paper we describe an assay with the fathead minnow (Pimephales promelas) in which AR antagonists can be identified through their ability to block an easily-observed AR-mediated response, production of male-specific secondary sex characteristics (e.g., cranial nuptial tubercles) in females exposed to the model AR agonist 17ί-trenbolone (TB). Exposure (via the water) to several well-characterized AR antagonists (flutamide, vinclozolin, cyproterone acetate) effectively inhibited induction of nuptial tubercles in female fathead minnows simultaneously-exposed for 14 d to water-borne TB (500 μg/L). Exposure of the fish to ammonia, a common environmental contaminant with no known HPG activity, did not block TB-induced nuptial tubercle formation in females. Inhibition of tubercle formation by TB in female fathead minnows provides the basis for a sensitive, specific and relatively simple assay to identify AR antagonists.
URLs/Downloads:
Use of Chemical Mixtures to Dfferentiate Mechanisms of Endocrine Action in a Small Fish Model