最近10年，对下丘脑-垂体-性腺轴的深入研究使人们对此有了进一步的认识，发现了2种新的下丘脑精氨酸-苯丙氨酸酰胺相关肽kisspeptin和促性腺激素抑制激素，这些物质有调节生殖轴的作用。Kisspeptins是下丘脑-垂体-性腺轴最有效的激活剂，Kisspeptin及其受体GPR54在促性腺激素释放激素神经元中表达，并调节其功能，可促进青春前期促性腺激素释放激素的释放和黄体生成素的分泌。kisspeptin/GPR54系统对于调节性成熟和生殖细胞的发育很重要。
土耳其Firat 大学医学院Haluk Kelestimur教授所在研究团队以表达促性腺激素释放激素的GT1-7细胞系为模型，研究发现精氨酸-苯丙氨酸酰胺相关肽促性腺激素抑制激素或精氨酸-苯丙氨酸酰胺相关肽1对kisspeptins激活的促性腺激素释放激素神经元激活有抑制作用，这种抑制作用的发挥不需要降低[Ca2+]i 。说明，精氨酸-苯丙氨酸酰胺相关肽3，1均参与下丘脑-垂体-性腺轴的调节作用。相关文章发表于2013年6月第18期《中国神经再生研究（英文版）》杂志上。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Neural Regeneration Research DOI: 10.3969/j.issn.1673-5374.2013.18.009
Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons Haluk
Kelestimur, Emine Kacar, Aysegul Uzun, Mete Ozcan, Selim Kutlu
The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.
