Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics
| Autor: | Skylar J. Ferrara, Dennis Bourdette, Thomas S. Scanlan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Central Nervous System
Male 0301 basic medicine Hypothalamo-Hypophyseal System Thyroid Hormones endocrine system medicine.medical_specialty endocrine system diseases Central nervous system Radioimmunoassay Thyroid Gland 030209 endocrinology & metabolism Endogeny Acetates Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Hypothyroidism Phenols Internal medicine Central hypothyroidism medicine Animals Sobetirome Research Articles business.industry Thyroid Hypothalamic–pituitary–thyroid axis Mice Inbred C57BL Thyroxine 030104 developmental biology medicine.anatomical_structure Pituitary Gland Triiodothyronine business Hormone |
| Zdroj: | Endocrinology. 159:2733-2740 |
| ISSN: | 1945-7170 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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