Angelopoulou Eleni, Inquimbert Perrine, Klosen Paul, Anderson Greg, Kalsbeek Andries, Simonneaux Valérie
University of Strasbourg, France.
University of Otago, New Zealand.
J Circadian Rhythms. 2021 Apr 15;19:4. doi: 10.5334/jcr.212.
Female reproductive success relies on proper integration of circadian- and ovarian- signals to the hypothalamic-pituitary-gonadal axis in order to synchronize the preovulatory LH surge at the end of the ovarian follicular stage with the onset of the main active period. In this study, we used a combination of neuroanatomical and electrophysiological approaches to assess whether the hypothalamic neurons expressing Arg-Phe amide-related peptide (RFRP-3), a gonadotropin inhibitory peptide, exhibit daily and estrous stage dependent variations in female mice. Furthermore, we investigated whether arginine vasopressin (AVP), a circadian peptide produced by the suprachiamatic nucleus regulates RFRP-3 neurons. The number of c-Fos-positive RFRP-3 immunoreactive neurons is significantly reduced at the day-to-night transition with no difference between diestrus and proestrus. Contrastingly, RFRP neuron firing rate is higher in proestrus as compared to diestrus, independently of the time of the day. AVP immunoreactive fibers contact RFRP neurons with the highest density observed during the late afternoon of diestrus and proestrus. Application of AVP increases RFRP neurons firing in the afternoon (ZT6-10) of diestrus, but not at the same time point of proestrus, indicating that AVP signaling on RFRP neurons may depend on circulating ovarian steroids. Together, these studies show that RFRP neurons integrate both daily and estrogenic signals, which downstream may help to properly time the preovulatory LH surge.
雌性生殖成功依赖于昼夜节律信号和卵巢信号与下丘脑-垂体-性腺轴的适当整合，以便在卵巢卵泡期结束时将排卵前促黄体生成素激增与主要活跃期的开始同步。在本研究中，我们结合神经解剖学和电生理学方法，评估表达促性腺激素抑制肽精氨酸-苯丙氨酸酰胺相关肽（RFRP-3）的下丘脑神经元在雌性小鼠中是否表现出每日和发情期依赖性变化。此外，我们研究了由视交叉上核产生的昼夜节律肽精氨酸加压素（AVP）是否调节RFRP-3神经元。c-Fos阳性RFRP-3免疫反应性神经元的数量在白天到夜晚的转变时显著减少，在间情期和发情前期之间没有差异。相反，与间情期相比，发情前期RFRP神经元的放电频率更高，与一天中的时间无关。AVP免疫反应性纤维与RFRP神经元接触，在间情期和发情前期的下午晚些时候观察到最高密度。应用AVP可增加间情期下午（ZT6-10）RFRP神经元的放电，但在发情前期的同一时间点则不然，这表明AVP对RFRP神经元的信号传导可能依赖于循环中的卵巢类固醇。总之，这些研究表明，RFRP神经元整合了每日信号和雌激素信号，这在下游可能有助于恰当地安排排卵前促黄体生成素激增的时间。
