Vasopressin regulation of the proestrous luteinizing hormone surge in wild-type and Clock mutant mice
Vasopressin regulation of the proestrous luteinizing hormone surge in wild-type and Clock mutant mice
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DOI：
10.1095/biolreprod.106.052845
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发表时间：
2006-11-01
影响因子：
3.6
通讯作者：
Takahashi, Joseph S.
中科院分区：
文献类型：
--
作者：
Miller, Brooke H.;Olson, Susan Losee;Takahashi, Joseph S.
雌性小鼠的排卵和发情周期受荷尔蒙和昼夜节律的控制。我们已经证明，具有核心昼夜节律基因时钟突变的小鼠具有异常的发情周期，并且由于下丘脑水平的缺陷，发情前期的下午没有黄体生成素(LH)激增。在目前的研究中，我们验证了加压素(AVP)可以作为昼夜节律信号来调节促黄体生成素释放的假说，并且这种信号在时钟突变中是缺失的。我们发现与野生型小鼠相比，时钟突变小鼠在视交叉上核(SCN)的AVP表达和在下丘脑的AVP 1a受体(AVPR1A)的表达减少。脑室内(i.c.v.)在发情前期下午注射AVP足以诱导黄体生成素的分泌，在500只时钟突变小鼠中达到高峰水平。AVP对时钟突变的LH峰的影响是由AVPR1A介导的，因为AVP和AVPR1A特异性拮抗剂的共同输入阻止了AVP诱导LH值的释放，尽管向野生型小鼠注入AVPR1A型拮抗剂未能阻止发情中的LH峰。这些结果表明，下丘脑AVP信号的减少在时钟突变小鼠中没有发情前黄体生成素峰起到了作用。这些结果也支持这样一种假设，即由SCN产生的AVP可能是调节黄体生成素释放的昼夜节律信号。
In the female mouse, ovulation and estrous cyclicity are under both hormonal and circadian control. We have shown that mice with a mutation in the core circadian gene Clock have abnormal estrous cycles and do not have a luteinizing hormone (LH) surge on the afternoon of proestrus due to a defect at the hypothalamic level. In the present study, we tested the hypotheses that vasopressin (AVP) can act as a circadian signal to regulate the proestrous release of LH, and that this signal is deficient in the Clock mutant. We found that Avp expression in the suprachiasmatic nucleus (SCN) and AVP 1a receptor (Avpr1a) expression in the hypothalamus is reduced in Clock mutant mice compared to wild-type mice. Intracerebroventricular (i.c.v.) injection of AVP on the afternoon of proestrus is sufficient to induce LH secretion, which reaches surge levels in 500 of Clock mutant mice. The effect of AVP on the Clock mutant LH surge is mediated by AVPR1A, as co-infusion of AVP and an AVPR1A-specific antagonist prevents AVP induction of LH release, although infusion of an AVPR1A antagonist into wild-type mice failed to prevent a proestrous LH surge. These results suggest that reduced hypothalamic AVP signaling plays a role in the absence of the proestrous LH surge in Clock mutant mice. The results also support the hypothesis that AVP produced by the SCN may be a circadian signal that regulates LH release.