The type 2 and type 3 iodothyronine deiodinases play important roles in coordinating development in Rana catesbeiana tadpoles

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
Endocrinology (Impact Factor: 4.64). 08/1997; 138(7):2989-97. DOI: 10.1210/en.138.7.2989
Source: PubMed

ABSTRACT In developing Rana catesbeiana tadpoles, the timing of the thyroid hormone (TH)-dependent metamorphic responses varies markedly among tissues. Yet at any one time these tissues are exposed to the same plasma concentration of TH, suggesting that TH action is regulated in part at the level of the peripheral tissues. A major factor in TH action is the intracellular level of the active TH, T3. This level is dependent not only on the plasma concentration of TH (mostly T4) but also on the intracellular activities of the type 2 5'-deiodinase (D2) and the type 3 5-deiodinase (D3), which are responsible, respectively, for generating and degrading T3. (D1 is not present in this species.) To determine whether differential expression of D2 and D3 among tissues could be a significant factor in the coordination of metamorphic events, the ontogenic profiles of the two enzyme activities and corresponding messenger RNA levels in most tissues of R. catesbeiana tadpoles have been documented. The profiles of D2 expression in tail, hindlimb, forelimb, intestine, skin, and eye differed markedly at both activity and messenger RNA levels, but it was notable that expression was invariably highest in a given tissue at the time of its major metamorphic change. D2 expression was very low in brain and heart and did not vary during development. D2 was not expressed in liver, kidney, or red blood cells. With the exception of red blood cells, D3 expression was detected in all tissues studied. Furthermore, it was evident that in tissues that expressed both deiodinase genes, the two expression profiles were comparable, indicating a potential for tight control of intracellular T3 levels. Direct evidence of the importance of the intracellular conversion of T4 to T3 for TH-dependent metamorphic events was obtained in tadpoles in which endogenous TH synthesis was blocked with methimazole, and the activities of D2 and D3 were inhibited by iopanoic acid. This treatment inhibited metamorphosis. The inhibition could be overcome by the concomitant administration of replacement levels of T3, but not T4. These results strongly support the view that coordinated development in amphibia depends in part on the tissue-specific expression patterns of the D2 and D3 genes, which ensure that the requisite level of intracellular T3 is attained in a given tissue, regardless of the current level of circulating TH, at the appropriate stage of metamorphosis.

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    ABSTRACT: We examined indices of thyroid development in tadpoles from ammonium perchlorate (AP)-exposed sites. Bullfrog (Rana catesbeiana) tadpoles collected from a reference site exhibited normal developmental features, with many completing metamorphoses. In contrast, tadpoles collected from the AP contaminated site exhibited a 5-fold lower hindlimb/snout-vent length ratio than tadpoles from the reference site. The volume of the thyroid gland was 2.5-fold larger in the tadpoles from the reference site, presumably because they had progressed to late prometamorphosis and early metamorphic climax. Premetamorphic western chorus frog tadpoles (Pseudacris triseriata) inhabiting an ephemeral pond contaminated with AP exhibited gross morphological abnormalities of the thyroid including colloid depletion and follicle cell hypertrophy. We conclude that tadpoles exposed to AP-contaminated pond water early in larval life exhibit delayed development ofthyroid-hormone sensitive structures. Additionally, there are abnormalities in the developing thyroid gland that seem to depend upon the window of AP exposure. The potential impact of thyroid disruption on development and reproduction in amphibian populations will be discussed.
    Multiple Stressor Effects in Relation to Declining Amphibian Populations, ASTM STP 1443, Edited by G. Linder, s. Krest, D. Sparling, E. Little, 01/2003: chapter Ammonium Perchlorate Disruption of Thyroid Function in Natural Amphibian Populations: Assessment and Potential Impact; ASTM International.
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    ABSTRACT: Our recent study showed that monocrotophos (MCP) pesticide disrupted the hypothalamic-pituitary-thyroid (HPT) axis in male goldfish (Carassius auratus); however, the effects of MCP on the thyroid system in female goldfish are remain unclear. In the present study, plasma thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels were evaluated in female goldfish exposed to 0.01, 0.10, and 1.00 mg/L of 40% MCP-based pesticide for 21 days in a semi-static exposure system. Expression profiles of HPT axis-responsive genes, including transthyretin (ttr), deiodinases (d1, d2, and d3), tshβ, thyrotropin-releasing hormone (trh), and corticotrophin-releasing hormone (crh), were determined. The results indicated that MCP decreased the plasma levels of total 3,3',5-triiodo-l-thyronine (TT3) and the ratio of TT3 to total 3,3',5,5'-l-thyroxine (TT4), and induced alternative expression of TH-related genes. Exposure to 0.01 and 0.10 mg/L MCP pesticide resulted in the up-regulation of ttr mRNA. The reduction of plasma TT3 levels was partly attributed to an increase in the metabolism of T3 in the liver, as revealed by the highly elevated hepatic d1 and d3 mRNA levels in the MCP treatment groups, and the expression of hepatic d3 showed a negative correlation with the plasma TT3/TT4 levels in females. Moreover, the plasma TSH levels were lower in females exposed to 0.01 and 0.10 mg/L MCP pesticide, whereas the up-regulation of tshβ mRNA levels was compensated by the decreased plasma TT3 levels. These results indicated that MCP had the potential to influence several pathways of HPT axis homeostasis in female goldfish.
    PLoS ONE 09/2014; 9(9):e108972. DOI:10.1371/journal.pone.0108972 · 3.53 Impact Factor
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