Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters
Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters
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DOI：
10.1073/pnas.232490799
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发表时间：
2002-12-10
影响因子：
11.1
通讯作者：
Nelson, RJ
中科院分区：
文献类型：
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作者：
Prendergast, BJ;Mosinger, B;Nelson, RJ
在季节性繁殖的哺乳动物中，大脑中的一种间隔计时机制通过触发对仲冬期间抑制短光周期的耐受性来控制生殖。神经机制负责的时间和诱导这种季节性时钟的光耐火性尚不清楚。利用cDNA微阵列技术和RT-PCR技术，我们鉴定出一类编码甲状腺素（T-4）结合蛋白（转甲状腺素、T-4结合球蛋白、白蛋白）的基因，这些基因的表达与短日照下的生殖难耐性有关。这些基因的下调与下丘脑T-4摄取减少有关，长时间的光周期处理可以逆转这种情况，恢复对短时间的反应性。正常甲状腺仓鼠的循环T-4浓度不随光反应状态变化，但阻断甲状腺功能加速了短时间内的光难反应。这些数据将下丘脑基因表达的变化与季节性时钟的功能输出联系起来。短日繁殖抑制仅在非繁殖季节后期依赖于T-4。在此期间，下丘脑中编码T-4结合蛋白的基因下调可能会限制静态T-4信号进入调节生殖的下丘脑靶组织，从而定时生殖功能的年度转变。下丘脑对T-4内流的自动调节可能是一个关键的细胞过程，参与了季节性生殖节律的产生和表达，并提示了一种以前未描述的神经靶点获得外周激素的机制。
An interval timing mechanism in the brain governs reproduction in seasonally breeding mammals by triggering refractoriness to inhibitory short photoperiods during midwinter. The neural mechanisms responsible for the timing and induction of photorefractoriness by this seasonal clock are unknown. Using cDNA microarrays and RT-PCR, we identified a class of genes encoding thyroxine (T-4)-binding proteins (transthyretin, T-4-binding globulin, albumin) whose expression is associated with reproductive refractoriness to short day lengths. Down-regulation of these genes was associated with reduced hypothalamic T-4 uptake, which was reversed by long-day photoperiod treatments that restored responsiveness to short days. Circulating T-4 concentrations did not vary with states of photoresponsiveness in euthyroid hamsters, but blockade of thyroid function accelerated the onset of photorefractoriness to short days. These data link changes in gene expression in the hypothalamus to the functional output of a seasonal clock. Reproductive inhibition in short days depends on T-4 only late in the nonbreeding season. Down-regulation of genes encoding T-4-binding proteins in the hypothalamus during this interval may restrict access of a static T-4 signal to hypothalamic target tissues that regulate reproduction, thereby timing annual transitions in reproductive function. Hypothalamic autoregulation of T-4 influx may constitute a critical cellular process involved in the generation and expression of seasonal reproductive rhythms and suggests a previously undescribed mechanism by which neural targets gain access to peripheral hormones.