Pulse and Surge Profiles of Luteinizing Hormone Secretion in the Mouse

Pulse and Surge Profiles of Luteinizing Hormone Secretion in the Mouse
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DOI:
10.1210/en.2016-1351
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发表时间:
2016-12-01
期刊:
影响因子:
4.8
通讯作者:
Herbison, Allan E.
Herbison, Allan E.
中科院分区:
医学2区
文献类型:
--
作者:
Czieselsky, Katja;Prescott, Mel;Herbison, Allan E.

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使用一种新的尾端出血程序和灵敏的ELISA法,我们在这里描述了在小鼠动情周期中黄体生成素的分泌模式;在去卵巢的小鼠中;在去卵巢的雌激素治疗的建模雌激素负反馈和正反馈的小鼠中;以及在表现出等位基因依赖的GnRH神经元数量减少的转基因GNR23小鼠中。在发情周期的所有阶段,黄体生成素都有明显的脉动分泌,发情、发情和发情小鼠的促黄体生成素脉冲频率约为每小时一个脉冲,但发情期的频率要低得多(每4小时不到一个脉冲)。卵巢切除导致基础和脉动的黄体生成素分泌显著增加,脉搏大约每21分钟出现一次。通过负反馈的慢性治疗,充填雌二醇的胶囊使黄体生成素脉冲频率恢复到完整的卵泡期水平,尽管脉冲幅度仍然较高。在发情前期的下午,发现黄体生成素高峰在4小时的范围内以高度可变的方式开始,持续3小时以上。相比之下,去卵巢、雌激素治疗、正反馈的小鼠在熄灯前大约0.5小时表现出相对一致的峰起。去性腺的野生型和杂合子GNR23(类似于200个GnRH神经元)雄性小鼠每60分钟出现一次黄体生成素脉冲。纯合的GNR23小鼠(类似于80个GnRH神经元)具有非常低的基础促黄体生成素浓度,但每90分钟继续表现出小幅度的促黄体生成素脉冲。这些研究首次在小鼠中描述了整个发情周期中促黄体生成素分泌的脉动和激增模式,并证明只有极少的促性腺激素释放激素神经元是促黄体生成素脉冲性分泌所必需的。
Using a new tail-tip bleeding procedure and a sensitive ELISA, we describe here the patterns of LH secretion throughout the mouse estrous cycle; in ovariectomized mice; in ovariectomized, estradiol- treated mice that model estrogen-negative and-positive feedback; and in transgenic GNR23 mice that exhibit allele-dependent reductions in GnRH neuron number. Pulsatile LH secretion was evident at all stages of the estrous cycle, with LH pulse frequency being approximately one pulse per hour in metestrous, diestrous, and proestrous mice but much less frequent at estrus (less than one pulse per 4 h). Ovariectomy resulted in substantial increases in basal and pulsatile LH secretion with pulses occurring approximately every 21 minutes. Chronic treatment with negative-feedback, estradiol-filled capsules returned LH pulse frequency to intact follicular phase levels, although pulse amplitude remained elevated. On the afternoon of proestrus, the LH surge was found to begin in a highly variable manner over a 4-hour range, lasting for more than 3 hours. In contrast, ovariectomized, estradiol-treated, positive-feedback mice exhibited a relatively uniform surge onset at approximately 0.5 hour prior to lights out. Gonadectomized wild-type and heterozygous GNR23 (similar to 200 GnRH neurons) male mice exhibited an LH pulse every 60 minutes. Homozygous GNR23 mice (similar to 80 GnRH neurons) had very low basal LH concentrations but continued to exhibit small amplitude LH pulses every 90 minutes. These studies provide the first characterization in mice of pulse and surge modes of LH secretion across the estrous cycle and demonstrate that very few GnRH neurons are required for pulsatile LH secretion.