Meeting Abstract

P3.69  Sunday, Jan. 6  Thyroid Hormone Induces Up-Regulation of Two Genes Sensitive to Endocrine Disruption During Amphibian Metamorphosis SUTTON, T.R.*; WOLFF, S.W.; HAVEN, T.S.; VELDHOEN, N.; HELBING, C.C.; PROPPER, C.R.; Northern Arizona University, Flagstaff, USA; Northern Arizona University, Flagstaff, USA; Northern Arizona University, Flagstaff, USA; University of Victoria, BC, Canada; University of Victoria, BC, Canada; Northern Arizona University, Flagstaff, USA trs228@nau.edu

Thyroid hormone (TH) is critical to developmental pathways and essential in the normal function of the cardiovascular, central nervous, digestive and reproductive systems. In amphibians, TH is vital to the reorganization of these systems during metamorphosis and involves reprogramming of gene expression. Our studies using microarrays found that expression of fibroblast activation protein alpha (FAPα) and corticotropin releasing hormone binding protein (CRHBP) were highly TH-responsive and disrupted by exposure to environmental contaminants. CRHBP has been shown to be an important modulator of amphibian metamorphic timing, and altered FAPα expression is linked to several human cancers. Expression of these genes is clearly under TH control during development, therefore it is important to gain a better understanding of the functional role they play in tissue organization. In order to further evaluate the TH sensitivity of these genes, we exposed Xenopus laevis to 0, 0.1, 1.0, 10, and 50nM of T3 for 48 and 72 hours and measured changes in mRNA abundance using real time PCR relative quantification. We compared the results to standard morphometric shifts in development. FAPα and CRHBP mRNA expression was increased as early as 48 hours as low as 10nM and 50nM T3, although the 10 and 50 nM doses did not differ from each other. By 72 hours post-exposure, FAPα mRNA levels were increased in a dose-dependent manner and sensitive to 1 nM T3. CRHBP also showed TH responsiveness at 72 hrs, with the lowest effective dose being 10 nM. These results indicate that FAPα and CRHBP are effective gene expression markers for thyroid sensitivity.