Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat
Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat
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DOI：
10.1016/j.mce.2006.07.002
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发表时间：
2006-09-26
影响因子：
4.1
通讯作者：
Tena-Sempere, M.
中科院分区：
文献类型：
--
作者：
Castellano, J. M.;Navarro, V. M.;Tena-Sempere, M.
Kisspeptins最近成为促性腺激素分泌和青春期开始的重要调节因子。这些功能主要通过刺激下丘脑促性腺激素释放激素（GnRH）分泌来进行。然而，Kiss-1生理学的相关方面，包括其刺激作用的个体发育和主要信号系统，仍有待充分阐明。为了解决这些问题，在出生后成熟的早期阶段监测kisspeptin-10对GnRH和LH分泌的影响，并评估大鼠青春期过渡沿着对kisspeptin敏感性的潜在变化。此外，kisspeptin诱导的GnRH分泌参与的信号级联反应，探讨了通过药理学阻断使用大鼠下丘脑外植体。尽管性不成熟，kisspeptin-10有效地引起GnRH释放离体和LH分泌体内在出生后发育的早期阶段（新生儿到青少年）。然而，LH对低剂量kisspeptin的反应性在青春期动物中增强。关于GnRH分泌，kisspeptin-10的刺激作用需要激活磷脂酶-C、动员细胞内Ca 2+和募集ERK 1/2和p38激酶，但在阻断2型环加氧酶和前列腺素合成后仍能保持。总之，我们目前的数据文件的个体发育，敏感性和细胞内信号的刺激作用kisspeptin在大鼠的GnRH/LH轴。虽然LH对低剂量kisspeptin的反应似乎在青春期增强，但kisspeptin能够在出生后成熟的早期阶段容易地激活GnRH系统。这些观察结果进一步强调了kisspeptin在正常和最终病理性的青春期时间安排中的重要作用。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Kisspeptins have recently emerged as essential regulators of gonadotropin secretion and puberty onset. These functions are primarily conducted by stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. However, relevant aspects of Kiss-1 physiology, including the ontogeny and major signaling systems of its stimulatory action, remain to be fully elucidated. To cover these issues, the effects of kisspeptin-10 on GnRH and LH secretion were monitored at early stages of postnatal maturation, and potential changes in the sensitivity to kisspeptin were assessed along the pubertal transition in the rat. In addition, the signaling cascades involved in kisspeptin-induced GnRH secretion were explored by means of pharmacological blockade using rat hypothalamic explants. Despite sexual immaturity, kisspeptin-10 potently elicited GnRH release ex vivo and LH secretion in vivo at early stages (neonatal to juvenile) of postnatal development. Yet, LH responsiveness to low doses of kisspeptin was enhanced in peri-pubertal animals. Concerning GnRH secretion, the stimulatory action of kisspeptin-10 required activation of phospholipase-C, mobilization of intracellular Ca2+ and recruitment of ERK1/2 and p38 kinases, but was preserved after blockade of type 2 cyclo-oxygenase and prostaglandin synthesis.,In summary, our present data document the ontogeny, sensitivity and intracellular signals for the stimulatory action of kisspeptin on the GnRH/LH axis in the rat. Although LH responses to low doses of kisspeptin appeared to be enhanced at puberty, kisspeptin was able to readily activate the GnRH system at early stages of postnatal maturation. These observations further stress the essential role of kisspeptin in normal, and eventually pathological, timing of puberty. (c) 2006 Elsevier Ireland Ltd. All rights reserved.