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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/R877    most recent 00101.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by García-G, C. Articles by Orozco, A. Search for Related Content PubMed PubMed Citation Articles by García-G, C. Articles by Orozco, A.

COMPARATIVE AND EVOLUTIONARY PHYSIOLOGY

3,5-Diiodothyronine in vivo maintains euthyroidal expression of type 2 iodothyronine deiodinase, growth hormone, and thyroid hormone receptor 1 in the killifish

¹Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, Universidad Nacional Autónoma de México, Querétaro, Mexico; and ²The Whitney Laboratory, University of Florida, St. Augustine, Florida

Submitted 12 February 2007 ; accepted in final form 16 May 2007

Until recently, 3,5-diiodothyronine (3,5-T₂) has been considered an inactive by-product of triiodothyronine (T₃) deiodination. However, studies from several laboratories have shown that 3,5-T₂ has specific, nongenomic effects on mitochondrial oxidative capacity and respiration rate that are distinct from those due to T₃. Nevertheless, little is known about the putative genomic effects of 3,5-T₂. We have previously shown that hyperthyroidism induced by supraphysiological doses of 3,5-T₂ inhibits hepatic iodothyronine deiodinase type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner as T₃ and T₄, suggesting a pretranslational effect of 3,5-T₂ (Garcia-G C, Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201–209, 2004). The question remains as to whether 3,5-T₂ would have effects under conditions similar to those that are physiological for T₃. To this end, intact killifish were rendered hypothyroid by administering methimazole. Groups of hypothyroid animals simultaneously received 30 nM of either T₃, reverse T₃, or 3,5-T₂. Under these conditions, we expected that, if it were bioactive, 3,5-T₂ would mimic T₃ and thus reverse the compensatory upregulation of D2 and tyroid receptor 1 and downregulation of growth hormone that characterize hypothyroidism. Our results demonstrate that 3,5-T₂ is indeed bioactive, reversing both hepatic D2 and growth hormone responses during a hypothyroidal state. Furthermore, we observed that 3,5-T₂ and T₃ recruit two distinct populations of transcription factors to typical palindromic and DR4 thyroid hormone response elements. Taken together, these results add further evidence to support the notion that 3,5-T₂ is a bioactive iodothyronine.

deiodinase type 2; thyroid hormone receptor 1; thyroid hormone response element; killifish