PI: Jennifer L. Specker; Institution: University of Rhode Island
For nearly four decades it was thought that glucocorticoid and mineralocorticoid actions of the major corticoid in teleost fish, cortisol, were mediated exclusively through Glucocorticoid receptors (GRs), owing to the absence of the mineralocorticoid, aldosterone. With the recent cloning of mineralocorticoid receptors (MRs) and 11b-hydroxysteroid dehydrogenases (11bHSD; enzymes which shuttle bioactive cortisol with its inactive metabolite cortisone), corticoid physiology in this class of vertebrates is now considered to be more complex than previously thought, however, the functions of 11bHSD and MR in fish are still not known. This study will test the hypothesis that enzymatic modulation of cortisol by 11bHSD is a pivotal mechanism regulating tissue-specific changes during summer flounder metamorphosis as they transform from symmetrical (larval) to asymmetrical (juvenile and adult) body forms. The progression of ontogenetic changes is timed with translocation of the right eye to the left side of the head, allowing for stage-specific experimentation that is otherwise difficult or impossible. Summer flounder are a marine flatfish with a remarkable capacity to osmoregulate at the larval stage. The PI and postdoctoral fellow will utilize two developmental phenomena of flounder metamorphosis. The first is the regulated increase in whole-body cortisol concentrations, followed by amplification of thyroid hormones. Cortisol and thyroid hormones modulate growth, differentiation, and ionoregulatory ability. The second is the ontogenetic shift in osmoregulatory function from the skin to the gills, characterized by degeneration and differentiation of salt-secreting chloride cells. This study will test whether the activity of 11bHSDs orchestrates tissue-specific actions of cortisol and will determine the developmental patterns of gene expression, endocrine regulation, and functional activity of 11bHSDs and relate these changes with location and abundance of GR and MR. Results from this study will provide important comparative data to understand the evolution of corticoid signaling in vertebrates. Further, this study will support the training and education of four undergraduates, will provide advanced training for a post-doctoral fellow, and will foster collaboration with colleagues at the University of Washington. 11bHSDs are also potential therapeutic targets in medicine and may also bind some xenobiotics. The research proposed here could lead to insights into improving the culture of marine fishes and understanding mechanisms of endocrine disruption in aquatic vertebrates.
