Involvement of thyrotropin in photoperiodic signal transduction in mice
Involvement of thyrotropin in photoperiodic signal transduction in mice
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DOI：
10.1073/pnas.0808952105
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发表时间：
2008-11-25
影响因子：
11.1
通讯作者：
Yoshimura, Takashi
中科院分区：
文献类型：
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作者：
Ono, Hiroko;Hoshino, Yuta;Yoshimura, Takashi
甲状腺激素激活酶(DIO2)和甲状腺激素失活酶(Dio3)在下丘脑内侧基底区(MBH)的局部甲状腺激素分解代谢调节鸟类和哺乳动物的季节性繁殖。最近对鸟类的功能基因组分析表明，长时间的日照会诱导脑下垂体结节(PT)产生促甲状腺激素，从而触发MBH的室管膜细胞(EC)中DIO2的表达。在哺乳动物中，夜间褪黑激素的分泌为含有高密度褪黑素受体的PT提供光周期的内分泌信号，但PT中的褪黑素信号与MBH中的甲状腺激素水平之间的接口尚不清楚。在这里，我们在小鼠身上提供了TSH参与光周期信号转导的证据。尽管大多数小鼠品系被认为是非季节性的，但在褪黑素熟练的CBA/N小鼠中观察到了强大的光周期反应，包括诱导TSHB(TSHβ亚单位)、CGA(TSHα亚单位)和DIO2的表达，以及降低dio3的表达。外源性褪黑素对C57BL/6J小鼠的上述基因表达的影响与CBA/N小鼠在短日照条件下观察到的结果相似。内皮细胞表达TSH受体(TSHR)，侧脑室注射TSH可诱导DIO2表达。最后，我们发现在TSHR缺失的小鼠中，褪黑素的应用并不影响TSHB、DIO2和DIO3的表达。综上所述，我们的发现表明，褪黑素对MBH中甲状腺激素水平的调节似乎涉及哺乳动物中的TSH。
Local thyroid hormone catabolism within the mediobasal hypothalamus (MBH) by thyroid hormone-activating (DIO2) and -inactivating (DIO3) enzymes regulates seasonal reproduction in birds and mammals. Recent functional genomics analysis in birds has shown that long days induce thyroid-stimulating hormone production in the pars tuberalis (PT) of the pituitary gland, which triggers DIO2 expression in the ependymal cells (EC) of the MBH. In mammals, nocturnal melatonin secretion provides an endocrine signal of the photoperiod to the PT that contains melatonin receptors in high density, but the interface between the melatonin signal perceived in the PT and the thyroid hormone levels in the MBH remains unclear. Here we provide evidence in mice that TSH participates in this photoperiodic signal transduction. Although most mouse strains are considered to be nonseasonal, a robust photoperiodic response comprising induced expression of TSHB (TSH beta subunit), CGA (TSH alpha subunit), and DIO2, and reduced expression of DIO3, was observed in melatonin-proficient CBA/N mice. These responses could not be elicited in melatonin-deficient C57BL/6J, but treatment of C57BL/6J mice with exogenous melatonin elicited similar effects on the expression of the above-mentioned genes as observed in CBA/N after transfer to short-day conditions. The EC was found to express TSH receptor (TSHR), and ICV injection of TSH induced DIO2 expression. Finally, we show that melatonin administration did not affect the expression of TSHB, DIO2, and DIO3 in TSHR-null mice. Taken together, our findings suggest that melatonin-dependent regulation of thyroid hormone levels in the MBH appears to involve TSH in mammals.