MP13 Aquatic Ecotoxicology
Monday, 14 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(CHO-1117-840033) Thyroid disruption in Xenopus by microsomal enzyme inducers: a multi-endpoint study with phenobarbital and PCN.

Chowdhury, M.¹, Holcombe, G.¹, Korte, J.¹, Kosian, P.¹, Linnum, A.¹, Bugge, M.¹, Tietge, J.¹, Degitz, S.¹, ¹ US Environmental Protection Agency, Duluth, MN, U.S.A.

ABSTRACT- Environmental chemicals can disrupt thyroid hormone (TH) homeostasis in animals by interacting with hypothalamus-pituitary-thyroid axis at various biochemical and molecular levels. The US Environmental Protection Agency (EPA) is developing an amphibian-based protocol for screening thyroid active chemicals. In mammals, induction of the microsomal enzyme uridine diphosphate glucuronosyltransferase (UDPGT) by xenobiotics results in increased thyroid hormone glucuronidation and elimination. However, it is unclear if the amphibian model shows a similar response. The objective of the present study was to test the model T₄ UDPGT-inducers, phenobarbital and pregnenolone-16- carbonitrile (PCN), to determine if the African clawed frog Xenopus laevis is sensitive to this mode of thyroid axis disruption. Stage-51 Xenopus larvae were exposed to phenobarbital (0, 125, 250, 500, 1000, and 1500 mg/L) or PCN (0, 37.5, 75, 150, 300, and 600 g/L) via the water. At day 21, we investigated developmental stages, thyroid gland histology, and mRNA steady state levels of proteins involved in thyroid hormone synthesis. Phenobarbital treatment resulted in concentration dependent delay in development and caused enlarged irregular follicles and follicular cell hypertrophy and hyperplasia in the thyroid gland. Treatment also resulted in increased expression of NIS (sodium iodide symporter), TPO (thyroperoxidase), TG (thyroglobulin), D2 (type II deiodinase), D3 (type III deiodinase) in the thyroid gland, although no changes in the pituitary TSH (thyroid stimulating hormone) were observed. Preliminary analysis of PCN data shows mild effects on larval development and thyroid morphology. Thus, the thyroid axis of X. laevis is influenced by phenobarbital as observed in mammals, but it is relatively less sensitive to PCN. We are currently developing biochemical and molecular tools to determine thyroid hormone glucuronidation in adult and larval Xenopus. (M. J. Chowdhury is a US NRC Research Associate. This abstract does not necessarily reflect US EPA policy).

Key words: thyroid disruption, Xenopus, glucuronidation, endocrine disrupting chemicals