Thyroid axis disruption by goitrogens: a molecular and functional approach

Guerreiro, Eduarda Mazagão

http://hdl.handle.net/10400.1/558

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Authors

Guerreiro, Eduarda Mazagão

Advisor(s)

Power, Deborah

Pinto, Patricia

Abstract(s)

The number of chemicals to which organisms are exposed as a consequence of environmental contamination by Industry and Agriculture is increasing. However, there is a severe lack of information about the biological effects of many frequently occurring chemicals. The present thesis is focused on the effects on the thyroid tissue of adult zebra fish of the antimicrobial agent Triclosan (TCS) which is frequently found in personnel hygiene products and foodstuff. After 21 days exposure of adult zebrafish to TCS (100 mg/kg/day) and the thyroid disruptor, Propylthiouracil (PTU, positive control) (5 mg/kg/day), histological observation of thyroid tissue in sections of the pharynx was performed. These observations indicated significant (p<0.05) increase in follicle areas coupled with the decrease of thyrocyte height (thyrocyte inactivation) in TCS treated zebrafish. In the PTU treated zebrafish only a reduction in thyrocyte activity was observed. In order to understand how the test chemical TCS might bring about its effect, the gene expression of Thyroglobulin (Tg), Thyroid Peroxidase (TPO), Sodium-Iodine Symporter (NIS) and Cathepsin B (CtsB) together with Thyroid Stimulating Hormone (TSH) in whole zebrafish head was determined using quantitative real-time Polymerase Chain Reaction (qRT-PCR). After sample normalization against the zebrafish spermatogenic glyceraldehyde-3-phosphate dehydrogenases (GAPDH-2), validated as reference gene for this study, a significant increase (p<0.05) in expression of TSH and NIS were detected. The expression of pituitary TSH increased in the PTU and TCS groups compared to the control group, while NIS expression only increased in the TCS treated zebrafish. For the remaining genes, no significant changes in gene expression were detected, maybe as a consequence of high individual variation. In summary, the results of the study indicate that the drug TCS at a concentration of 100 mg/kg/day for 21 days appears to influence TH synthesis. The increase in TSH and NIS transcription coupled to the inactivation of the thyroid tissue observed in this work, are indicative of effects caused by a reduction in circulating THs. It remains to be established the mechanism by which TCS reduces thyroid tissue activity in adult zebra fish.