A Multispecies Investigation of Thyroid Hormone Disruption PDF Download

Author: Kyla Marie Walter
Publisher:
ISBN: 9780438630222
Category :
Languages : en
Pages :

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Book Description
Thyroid hormones (THs) are essential for the proper development, growth and function of several organ systems, including the nervous, cardiovascular, and musculoskeletal systems. THs also contribute to homeostatic processes throughout life such as energy balance, thermoregulation, and endocrine regulation. Many environmental chemicals are suspected to disrupt the regulation of circulating TH concentrations and/or alter normal TH signaling. Thus, TH disruption is widely postulated as a mechanism by which environmental chemicals may cause adverse physiological outcomes. However, several gaps in our understanding of TH action and TH disruption have limited the development of predictive endpoints to screen chemicals for TH disruption. The five chapters contained herein investigate the use of two alternative models for studying TH disruption: larval zebrafish (Danio rerio) and housecats with naturally occurring hyperthyroidism. Zebrafish have been proposed as a promising model for studying TH-dependent mechanisms of neurodevelopment, screening chemicals for TH disrupting activity, and elucidating the adverse outcome pathways by which TH-disrupting chemical interfere with neurodevelopment. In Chapters 2-4, I characterized the impact of TH disruption in larval zebrafish. Several endpoints exhibited sensitivity to TH disruption including mRNA expression of core TH signaling genes, teratology, photomotor swimming behavior, and oligodendrocyte numbers in the spinal cord. These findings have significant implications for adapting zebrafish as a model for chemical screening and mechanistic studies of TH disrupting chemicals. In Chapter 5, I investigated the association between exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDEs), two chemical families suspected to cause TH disruption, and the development of feline hyperthyroidism. I demonstrated that the sum total PBDE concentrations in our feline samples were approximately 50 times greater than concentrations previously reported in the human population from a geographically similar area, and I identified four PBDE congeners (BDE17, BDE100, BDE47, and BDE49) and five PCB congeners (PCB131, PCB153, PCB174, PCB180, and PCB196) with significantly higher concentrations in hyperthyroid cats compared to control cats. Domestic housecats, with their elevated exposure to PBDEs, may serve as sentinels for the adverse health effects associated with exposure to these environmental pollutants.