Circadian Function in Multiple Cell Types Is Necessary for Proper Timing of the Preovulatory LH Surge.

Circadian Function in Multiple Cell Types Is Necessary for Proper Timing of the Preovulatory LH Surge.
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DOI:
10.1177/0748730419873511
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发表时间:
2019-12
影响因子:
3.5
通讯作者:
Bittman, Eric L.
Bittman, Eric L.
中科院分区:
生物学3区
文献类型:
--
作者:
Bittman, Eric L.

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排卵前促黄体生成激素(LH)激增的时间是由昼夜节律系统决定的,它发生在雌性小鼠发情前期的晚上。控制LH峰期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是必需的或足以解释排卵的昼夜节律控制。在其他细胞类型中,证据还表明前腹侧室周核(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,其放电直接负责垂体前叶LH的放电。目前的研究使用卵巢切除,雌二醇处理的准备,以确定关键的细胞类型,其时钟功能是至关重要的LH分泌的时间。正如预期的那样,LH峰发生在对照小鼠的ZT 12时或之后不久。在进一步确认昼夜节律控制中,tau突变动物中的激增提前了2小时。在AVPCre、KissCreBAC和GnRHCreBAC小鼠中,通过条件性删除Bmal1,浪涌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的浪涌逆转。Kiss1或GnRH神经元中Bmal1的条件性缺失对运动节律没有明显影响,但AVP神经元的靶向对昼夜节律产生可变影响,并不总是对应于LH分泌阶段的变化。结果表明,在多种细胞类型的昼夜节律功能是必要的适当时机的LH峰。
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.
DOI: 10.1371/journal.pone.0036119
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