Lampreys represent a key group of vertebrate animals in which many hypotheses concerning the evolution of steroid hormones and their receptors can be tested. This study will begin to test these hypotheses through determination of the structures, receptors, and functionality of unusual steroids in the sea lamprey (Petromyzon marinus). The gonads of the lamprey, one of only two groups of jawless fishes still alive today, are morphologically similar and undergo the same developmental processes as those of teleost (bony) fish. However, unlike teleosts, no steroids in lamprey have been linked to specific physiological functions. It has been hypothesized that androgens, a class of steroids normally associated with male reproduction, are not functional hormones in lampreys, and that vertebrate androgen receptors evolved from an ancestral estrogen receptor only after jawless vertebrates diverged from jawed vertebrates. However, the lack of evidence for the functionality of conventional androgens and the presence of their corresponding receptors may be explained by the alternative hypothesis that sea lampreys utilize unusual androgens and other unusual forms of sex steroids. This proposed study would focus the search for functional sex steroids in lamprey on those with an additional hydroxyl group on carbon 15 of the four-ring steroid structure, and not on typical mammalian or teleost steroids. The ultimate goal is to determine whether steroids with a 15a-hydroxyl group are functional sex hormones in the sea lamprey. In particular, this hypothesis will be tested by: (1) Confirming that sea lamprey gonads produce 15a-hydroxylated steroids; (2) Documenting changes in circulatory 15a-hydroxylated steroids in response to natural maturation; (3) Determining how plasma concentrations of 15a-hydroxylated steroids change in response to administration of lamprey GnRH I and GnRH III, which are known to stimulate maturation; and (4) Characterizing the binding properties of hypothesized receptors for 15a-hydroxylated steroids. Anticipated results from this study may also have significant implications in management and conservation of the sea lamprey, which is both a highly destructive pest species in the Great Lakes and an endangered species prized as a delicacy in Europe. The PI will promote teaching and training by involving a post-doctoral fellow, a Native American graduate student, several undergraduate students, and will include high-school students from an economically disadvantaged region.
Structure and Corresponding Receptors of Atypical Steroids in Sea Lamprey