Gottsch M L, Cunningham M J, Smith J T, Popa S M, Acohido B V, Crowley W F, Seminara S, Clifton D K, Steiner R A
Department of Physiology & Biophysics Health Sciences Building, G-424 School of Medicine University of Washington, Box 357290, 1959 Northeast Pacific Street, Seattle, Washington 98195-7290, USA.
Endocrinology. 2004 Sep;145(9):4073-7. doi: 10.1210/en.2004-0431. Epub 2004 Jun 24.
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.
亲吻素是KiSS-1基因的产物，它与一种名为GPR54的G蛋白偶联受体结合。GPR54基因的突变或靶向破坏会导致人类和小鼠出现低促性腺激素性性腺功能减退，这表明亲吻素信号传导可能对促性腺激素分泌的调节很重要。为了研究亲吻素-54（ metastin）和亲吻素-10（具有生物活性的C末端十肽）对小鼠促性腺激素分泌的影响，我们将亲吻素直接注入小鼠大脑侧脑室，并证明这两种肽都能刺激促黄体生成素（LH）的分泌。对亲吻素-54的进一步表征表明，它在低至1飞摩尔的剂量下就能刺激LH和促卵泡生成素（FSH）的分泌；此外，这种作用被强效促性腺激素释放激素（GnRH）拮抗剂阿昔林预处理所阻断。为了更多地了解亲吻素的功能解剖结构，我们绘制了下丘脑KiSS-1 mRNA的分布图。我们观察到，KiSS-1 mRNA在下丘脑参与促性腺激素分泌神经内分泌调节的区域表达，包括室旁前腹核、室旁核和弓状核。我们得出结论，亲吻素-GPR54信号传导可能是控制下丘脑GnRH分泌的下丘脑神经回路的一部分。
