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Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis
Citation:
STERNBERG, R. M., J. J. KORTE, S. M. MOEN, K. R. THOEMKE, AND J. E. TIETGE. Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis. Presented at SETAC Annual Meeting, Tampa, FL, November 16 - 20, 2008.
Impact/Purpose:
The results of this effort not only contribute to our basic understanding of the endocrinology of the HPT axis of anuran larvae, but also could be incorporated into an HPT systems model to serve as the framework for predicting the consequences of HPT perturbation by TDCs on the whole organism.
Description:
Environmentally-relevant chemicals such as perchlorate have the ability to disrupt the hypothalamo-pituitary-thyroid (HPT) axis of exposed individuals. Larval anurans are a particularly suitable model species for studying the effects of thyroid-disrupting chemicals (TDCs) because thyroid hormone (TH) is an important mediator of metamorphosis. Since a basic knowledge of the underlying endocrinology of the HPT axis of larval anurans is necessary for predicting how the axis may respond to perturbation by TDCs, we examined one of many unanswered questions regarding the larval anuran HPT axis: how do pituitary thyroid-stimulating hormone (TSH) gene expression levels and plasma TSH protein concentrations increase in concert with plasma concentrations of TH during metamorphosis? We used Xenopus laevis pituitary cultures to examine the hypothesis that the set-point for negative feedback on pituitary TSH release by TH changes during metamorphosis to allow for this seemingly paradoxical, concurrent rise in TH and TSH. Pituitaries from X. laevis tadpoles (NF stages 54 through 66) were cultured in media containing increasing, physiologically-relevant concentrations of thyroxine (T4). Media for individual pituitaries were collected and analyzed for TSH via Western blotting. Results indicated that pituitaries from tadpoles in the earlier stages of TH-dependent metamorphosis were more sensitive to T4-induced inhibition of TSH release than pituitaries from tadpoles in the later stages of TH-dependent metamorphosis. This pattern of in vitro pituitary sensitivity to T4 correlated well with in vivo circulating concentrations of T4 and TSH: both T4 and TSH remain low during the early stages of TH-dependent metamorphosis, rise simultaneously during later stages, and then fall towards the end of metamorphosis. Collectively, this in vitro and in vivo data provide support for the hypothesis that the set-point for negative feedback control of TSH release by T4 increases as metamorphosis progresses allowing for the concomitant rise in plasma concentrations of TSH and T4. The results of this effort not only contribute to our basic understanding of the endocrinology of the HPT axis of anuran larvae, but also could be incorporated into an HPT systems model to serve as the framework for predicting the consequences of HPT perturbation by TDCs on the whole organism.