Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction
Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction
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DOI：
10.1210/en.2007-0316
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Morgan, Peter J.
中科院分区：
文献类型：
--
作者：
Barrett, Perry;Ebling, Francis J. P.;Morgan, Peter J.
许多动物在生理上表现出的季节性适应涉及生物计时和特定神经内分泌系统之间的界面，但这种界面的分子基础尚不清楚。在西伯利亚仓鼠的这项研究中，我们表明，甲状腺激素在下丘脑的可用性是一个关键的决定因素，季节性转变。编码III型脱碘酶（Dio 3）的基因的表达和体内Dio 3活性（T-4和T-3的催化）受光周期的动态和时间调节，与短光周期下丘脑T3浓度的损失一致。暴露于短光周期的雄性仓鼠下丘脑中T3的慢性替代，从而绕过位于第三脑室室管膜细胞中的合成或分解代谢脱碘酶，防止了短日生理学的发生：仓鼠保持了长日体重表型，并且没有经历睾丸和附睾退化。然而，毛皮换羽的冬季大衣没有受到影响。II型脱碘酶基因的表达不受光周期在这些仓鼠。总的来说，这些数据表明下丘脑DIO 3和T-3催化剂在哺乳动物体重和生殖的季节性周期中起关键作用。
Seasonal adaptations in physiology exhibited by many animals involve an interface between biological timing and specific neuroendocrine systems, but the molecular basis of this interface is unknown. In this study of Siberian hamsters, we show that the availability of thyroid hormone within the hypothalamus is a key determinant of seasonal transitions. The expression of the gene encoding type III deiodinase ( Dio3) and Dio3 activity in vivo ( catabolism of T-4 and T-3) is dynamically and temporally regulated by photoperiod, consistent with the loss of hypothalamic T3 concentrations under short photoperiods. Chronic replacement of T3 in the hypothalamus of male hamsters exposed to short photoperiods, thus bypassing synthetic or catabolic deiodinase enzymes located in cells of the ependyma of the third ventricle, prevented the onset of shortday physiology: hamsters maintained a long- day body weight phenotype and failed to undergo testicular and epididymal regression. However, pelage moult to a winter coat was not affected. Type II deiodinase gene expression was not regulated by photoperiod in these hamsters. Collectively, these data point to a pivotal role for hypothalamic DIO3 and T-3 catabolism in seasonal cycles of body weight and reproduction in mammals.