Journal article
S. Ferrara, D. Bourdette, T. Scanlan
Endocrinology, 2018
Endocrinology, 2018
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APA
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Ferrara, S., Bourdette, D., & Scanlan, T. (2018). Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics. Endocrinology.
Chicago/Turabian
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Ferrara, S., D. Bourdette, and T. Scanlan. “Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics.” Endocrinology (2018).
MLA
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Ferrara, S., et al. “Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics.” Endocrinology, 2018.
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@article{s2018a,
title = {Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics.},
year = {2018},
journal = {Endocrinology},
author = {Ferrara, S. and Bourdette, D. and Scanlan, T.}
}
Abstract
Thyromimetics represent a class of experimental drugs that can stimulate tissue-selective thyroid hormone action. As such, thyromimetics should have effects on the hypothalamic-pituitary-thyroid (HPT) axis, but details of this action and the subsequent effects on systemic thyroid hormone levels have not been reported to date. Here, we compare the HPT-axis effects of sobetirome, a well-studied thyromimetic, with Sob-AM2, a newly developed prodrug of sobetirome that targets sobetirome distribution to the central nervous system (CNS). Similar to endogenous thyroid hormone, administration of sobetirome and Sob-AM2 suppress HPT-axis gene transcript levels in a manner that correlates to their specific tissue distribution properties (periphery vs CNS, respectively). Dosing male C57BL/6 mice with sobetirome and Sob-AM2 at concentrations ≥10 μg/kg/d for 29 days induces a state similar to central hypothyroidism characterized by depleted circulating T4 and T3 and normal TSH levels. However, despite the systemic T4 and T3 depletion, the sobetirome- and Sob-AM2-treated mice do not show signs of hypothyroidism, which may result from the presence of the thyromimetic in the thyroid hormone-depleted background.
