Developmental Changes in GnRH Release in Response to Kisspeptin Agonist and Antagonist in Female Rhesus Monkeys (Macaca mulatta): Implication for the Mechanism of Puberty
Developmental Changes in GnRH Release in Response to Kisspeptin Agonist and Antagonist in Female Rhesus Monkeys (Macaca mulatta): Implication for the Mechanism of Puberty
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DOI：
10.1210/en.2011-1565
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发表时间：
2012-02-01
期刊：
影响因子：
4.8
通讯作者：
Terasawa, Ei
中科院分区：
文献类型：
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作者：
Guerriero, Kathryn A.;Keen, Kim L.;Terasawa, Ei
Kisspeptin （KP）和KP-1受体（KISS1R）已成为控制青春期的重要上游调节因子。然而，KP-KISS1R的发育变化如何促进青春期GnRH释放的增加仍然是未知的。在这项研究中，我们使用微透析方法检测了KP激动剂人KP-10 （hKP-10）和KP拮抗剂肽234对青春期前和青春期卵巢完整的雌性恒河猴体内GnRH释放的影响。我们发现，直接将hKP-10注入下丘脑内侧基底区和柄-中隆起区以剂量响应的方式刺激GnRH释放，而肽234在两个发育阶段均抑制GnRH释放。由于在灵长类动物中，卵巢类固醇对GnRH释放的反馈在青春期开始后变得突出，因此我们进一步研究了卵巢类固醇是否会改变GnRH对hKP-10的反应。结果表明，卵巢切除术可以消除hkp -10诱导的GnRH释放的刺激，但不能消除青春期前的猴子。此外，在去卵巢的青春期猴子中替代雌二醇导致hkp -10诱导的GnRH释放部分恢复。总之，这些结果表明，除了我们之前报道的青春期KP-54释放增加外，kiss1r介导的机制也有助于青春期GnRH释放的增加，并且GnRH对KP的反应存在从卵巢类固醇依赖型到依赖型的机制转换。（内分泌学153:825-836,2012）
Kisspeptin (KP) and KP-1 receptor (KISS1R) have emerged as important upstream regulators in the control of puberty. However, how developmental changes in KP-KISS1R contribute to the pubertal increase in GnRH release still remains elusive. In this study, we examined the effects of the KP agonist, human KP-10 (hKP-10), and the KP antagonist, peptide 234, on in vivo GnRH release in prepubertal and pubertal ovarian-intact female rhesus monkeys using a microdialysis method. We found that direct infusion of hKP-10 into the medial basal hypothalamus and stalk-median eminence region stimulated GnRH release in a dose-responsive manner, whereas infusion of peptide 234 suppressed GnRH release in both developmental stages. Because ovarian steroid feedback on GnRH release becomes prominent after the initiation of puberty in primates, we further examined whether ovarian steroids modify the GnRH response to hKP-10. Results demonstrate that the hKP-10-induced stimulation of GnRH release was eliminated by ovariectomy in pubertal, but not prepubertal, monkeys. Furthermore, replacement of estradiol into ovariectomized pubertal monkeys resulted in a partial recovery of the hKP-10-induced GnRH release. Collectively, these results suggest that a KISS1R-mediated mechanism, in addition to the pubertal increase in KP-54 release we previously reported, contributes to the pubertal increase in GnRH release and that there is a switch from an ovarian steroid-independent to -dependent mechanism in the response of GnRH to KP. (Endocrinology 153: 825-836, 2012)