A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
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DOI：
10.1210/en.2004-0431
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Steiner, RA
中科院分区：
文献类型：
--
作者：
Gottsch, ML;Cunningham, MJ;Steiner, RA
Kisspeptins是KiSS-1基因的产物，它与G蛋白偶联受体GPR 54结合。GPR 54基因的突变或靶向破坏导致人类和小鼠的低促性腺激素性性腺功能减退症，这表明kisspeptin信号传导可能对促性腺激素分泌的调节很重要。为了研究kisspeptin-54（metastin）和kisspeptin-10（生物活性C-末端十肽）对小鼠促性腺激素分泌的影响，我们将kisspeptin直接注入大脑的侧脑室，并证明这两种肽刺激LH分泌。kisspeptin-54的进一步表征表明，它刺激LH和FSH分泌，剂量低至1 fmol;此外，这种作用被证明是阻断预处理与acyline，一种有效的GnRH拮抗剂。为了了解更多关于kisspeptins的功能解剖，我们绘制了KiSS-1 mRNA在下丘脑中的分布。我们观察到KiSS-1 mRNA在下丘脑涉及促性腺激素分泌的神经内分泌调节的区域中表达，包括前腹侧室周核、室周核和弓状核。我们的结论是，kisspeptin-GPR 54信号可能是下丘脑电路的一部分，支配下丘脑分泌的GnRH。
Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.