"Androgen receptors in fishes, endocrine, toxicological and evolutionary significance"

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Androgens, or male hormones, are essential for sexual development and function in both males and females of all vertebrates. The effects of androgens are mediated through androgen receptors that are thought to be conserved in all jawed vertebrates. Only teleost fishes are known to possess two androgen receptors. This likely occurred as a result of a genome duplication after the split of teleost fishes from other jawed vertebrates. However, not all teleost fishes have retained two androgen receptors and the function of the second distinct receptor remains an enigma. This research proposes to address three fundamental questions associated with androgen receptor regulation in fishes. The first question is "what is the endocrine function and signaling mechanism of two androgen receptors in those species that possess them?" This will be examined by determining the mechanism of signal transduction by either knocking down receptor expression in cell culture, or examining the function of the receptors in reporter gene bioassays. This will in turn require an understanding of the responsive elements that bind the receptor upstream of androgen-regulated genes - an area completely unexplored in fishes. The second question, "what is the evolutionary advantage of having two receptors?", will be examined by evaluating the reproductive traits of fishes with either just one, or two androgen receptors. This will entail developing a rapid molecular biology screening strategy for both receptors, and applying this to a wide range of diverse fish species. Finally, given the many reproductive-endocrine disrupting substances that are known to enter the environment, "we seek to know what the toxicological significance of two androgen receptors could be?" This will be examined by comparing the binding both receptors to known endocrine toxicants, examining the effects of those compounds on androgen-regulated gene products in cell culture, and by comparing the responses of two species of fish, with either one, or two receptors. This research will grow our understanding of the evolution of fishes and will provide knowledge and tools to better predict and diagnose impacts on our environment.