The timing of the preovulatory surge of luteinizing hormone (LH), which occurs on the evening of proestrus in female mice, is determined by the circadian system. The identity of cells that control the phase of the LH surge is unclear: evidence supports a role of arginine vasopressin (AVP) cells of the suprachiasmatic nucleus (SCN), but it is not known whether vasopressinergic neurons are necessary or sufficient to account for circadian control of ovulation. Among other cell types, evidence also suggests important roles of circadian function of kisspeptin cells of the anteroventral periventricular nucleus (AvPV) and gonadotropin-releasing hormone (GnRH) neurons of the preoptic area (POA), whose discharge is immediately responsible for the discharge of LH from the anterior pituitary. The present studies used an ovariectomized, estradiol-treated preparation to determine critical cell types whose clock function is critical to the timing of LH secretion. As expected, the LH surge occurred at or shortly after ZT12 in control mice. In further confirmation of circadian control, the surge was advanced by 2 h in tau mutant animals. The timing of the surge was altered to varying degrees by conditional deletion of Bmal1 in AVPCre, KissCreBAC, and GnRHCreBAC mice. Excision of the mutant Cnsk1e (tau) allele in AVP neurons resulted in a reversion of the surge to the ZT12. Conditional deletion of Bmal1 in Kiss1 or GnRH neurons had no noticeable effect on locomotor rhythms, but targeting of AVP neurons produced variable effects on circadian period that did not always correspond to changes in the phase of LH secretion. The results indicate that circadian function in multiple cell types is necessary for proper timing of the LH surge.

中文翻译：

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多种细胞类型的昼夜节律功能对于排卵前 LH 激增的适当时机是必要的。

雌性小鼠在发情前期晚上发生的促黄体生成素 (LH) 排卵前激增的时间是由昼夜节律系统决定的。控制 LH 激增阶段的细胞的身份尚不清楚：证据支持视交叉上核 (SCN) 的精氨酸加压素 (AVP) 细胞的作用，但尚不清楚加压素能神经元是否必要或足以解释昼夜节律控制排卵。在其他细胞类型中，证据还表明前腹侧脑室周围核 (AvPV) 的 Kisspeptin 细胞和视前区 (POA) 的促性腺激素释放激素 (GnRH) 神经元的昼夜节律功能的重要作用，其放电直接负责LH来自垂体前叶。本研究使用卵巢切除术，雌二醇处理的制剂，以确定其时钟功能对 LH 分泌时间至关重要的关键细胞类型。正如预期的那样，在对照小鼠中，LH 激增发生在 ZT12 时或之后不久。为了进一步证实昼夜节律控制，tau 突变动物的激增提前了 2 小时。通过有条件地删除 AVPCre、KissCreBAC 和 GnRHCreBAC 小鼠中的 Bmal1，激增的时间发生了不同程度的改变。切除 AVP 神经元中的突变 Cnsk1e (tau) 等位基因导致 ZT12 的激增逆转。Kiss1 或 GnRH 神经元中 Bmal1 的条件性删除对运动节律没有明显影响，但 AVP 神经元的靶向作用对昼夜节律产生不同的影响，这并不总是对应于 LH 分泌阶段的变化。