Daily and Estral Regulation of RFRP-3 Neurons in the Female Mice.
Daily and Estral Regulation of RFRP-3 Neurons in the Female Mice.
复制标题
雌性小鼠RFRP-3神经元的日常和发情调节。
DOI：
10.5334/jcr.212
复制
发表时间：
2021-04-15
影响因子：
--
通讯作者：
Simonneaux V
中科院分区：
文献类型：
--
作者：
Angelopoulou E;Inquimbert P;Klosen P;Anderson G;Kalsbeek A;Simonneaux V
女性生殖的成功依赖于昼夜节律和卵巢信号与下丘脑-垂体-性腺轴的适当整合，以使卵泡期结束时排卵前的LH激增与主要活跃期的开始同步。在这项研究中，我们采用神经解剖学和电生理学相结合的方法来评估雌性小鼠下丘脑神经元表达Arg-Phe酰胺相关肽（RFRP-3）（一种促性腺激素抑制肽）是否表现出每日和发情期依赖性变化。此外，我们研究了精氨酸抗利尿激素（AVP），一种由视交叉上核产生的昼夜节律肽是否调节RFRP-3神经元。c- fos阳性RFRP-3免疫反应神经元的数量在日-夜过渡期间显著减少，在发情期和发情前期无差异。相比之下，与一天中的时间无关，RFRP神经元在发情期的放电率高于发情期。AVP免疫反应纤维接触RFRP神经元的密度在发情和发情前的下午晚些时候最高。AVP的应用增加了RFRP神经元在发情下午（ZT6-10）的放电，而不是在发情前的同一时间点，表明AVP在RFRP神经元上的信号可能依赖于卵巢类固醇循环。总之，这些研究表明RFRP神经元整合了日常和雌激素信号，其下游可能有助于适当地控制排卵前LH激增的时间。
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.