PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly, France.
Department of Arctic and Marine Biology, University of Tromsø, Tromsø, Norway.
J Neuroendocrinol. 2019 Aug;31(8):e12775. doi: 10.1111/jne.12775. Epub 2019 Aug 8.
In mammals, melatonin is responsible for the synchronisation of seasonal cycles to the solar year. Melatonin is secreted by the pineal gland with a profile reflecting the duration of the night and acts via the pituitary pars tuberalis (PT), which in turn modulates hypothalamic thyroid hormone status via seasonal changes in the production of locally-acting thyrotrophin. Recently, we demonstrated that, in the Soay sheep, photoperiodic induction of Tshb expression and consequent downstream hypothalamic changes occur over a narrow range of photoperiods between 12 and 14 hours in duration. In the present study, we aimed to extend our molecular characterisation of this pathway, based on transcriptomic analysis of photoperiodic changes in the pituitary and hypothalamus of ovariectomised, oestradiol-implanted Ile-de-France ewes. We demonstrate that photoperiodic treatments applied before the winter solstice elicit two distinctive modes of accelerated reproductive switch off compared to ewes held on a simulated natural photoperiod, with shut-down occurring markedly faster on photoperiods of 13 hours or more than on photoperiods of 12 hours and less. This pattern of response was reflected in gene expression profiles of photoperiodically sensitive markers, both in the PT (Tshb, Fam150b, Vmo1, Ezh2 and Suv39H2) and in tanycytes (Tmem252 and Dct). Unexpectedly, the expression of Dio2 in tanycytes did not show any noticeable increase in expression with lengthening photoperiods. Finally, the expression of Kiss1, the key activator of gonadotrophin-releasing hormone release, was proportionately decreased by lengthening photoperiods, in a pattern that correlated strongly with gonadotrophin suppression. These data show that stepwise increases in photoperiod lead to graded molecular responses at the level of the PT, a progressive suppression of Kiss1 in the hypothalamic arcuate nucleus and luteinising hormone/follicle-stimulating hormone release by the pituitary, despite apparently unchanged Dio2 expression in tanycytes. We hypothesise that this apparent discontinuity in the seasonal neuroendocrine response illustrates the transient nature of the thyroid hormone-mediated response to long days in the control of circannual timing.
在哺乳动物中，褪黑素负责将季节性周期与太阳年同步。褪黑素由松果体分泌，其分泌模式反映了夜间的持续时间，并通过垂体中间部（PT）发挥作用，垂体中间部通过季节性变化产生局部作用的促甲状腺激素来调节下丘脑甲状腺激素状态。最近，我们证明在斯澳羊中，Tshb 表达的光周期诱导以及随后的下丘脑变化发生在 12 至 14 小时持续时间的狭窄光周期范围内。在本研究中，我们旨在基于对去卵巢、雌二醇植入的 Ile-de-France 母羊垂体和下丘脑的光周期变化的转录组分析，扩展我们对该途径的分子特征描述。我们证明，在冬至之前施加的光周期处理与在模拟自然光周期下饲养的母羊相比，会引发两种不同的加速繁殖关闭模式，与 12 小时或更短的光周期相比，关闭速度明显更快。这种反应模式反映在光周期敏感标记物的基因表达谱中，无论是在 PT（Tshb、Fam150b、Vmo1、Ezh2 和 Suv39H2）还是在室管膜细胞（Tmem252 和 Dct）中。出乎意料的是，Dio2 在室管膜细胞中的表达并没有随着光周期的延长而明显增加。最后，关键的促性腺激素释放激素释放激活剂 Kiss1 的表达随着光周期的延长而相应减少，这种模式与促性腺激素抑制密切相关。这些数据表明，PT 水平的分级分子反应随着光周期的逐步增加而增加，尽管在室管膜细胞中 Dio2 的表达明显不变，但下丘脑弓状核中 Kiss1 的表达逐渐降低，垂体中黄体生成素/卵泡刺激素的释放。我们假设这种季节性神经内分泌反应的不连续性说明了在控制年节律计时中，长日照对甲状腺激素介导反应的短暂性质。
