Kisspeptin 234 is a potent kisspeptin receptor (KISS1/GPR54) antagonist composed of ten amino acids[1]. By binding to GPR54, Kisspeptin 234 inhibits the stimulatory effect of kisspeptin on the hypothalamic-pituitary-gonadal (HPG) axis, reduces the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, and subsequently suppresses pituitary luteinizing hormone (LH) release[2]. Kisspeptin 234 is commonly used in research areas such as the onset of puberty, reproductive disorders (e.g., polycystic ovary syndrome), and cardiovascular diseases[3,4].
In vitro, treatment of four human endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) with Kisspeptin 234 (100nM) for 24h significantly promoted cell migration ability. Treatment of RL95-2 cells with Kisspeptin 234 (100nM) for 2h significantly increased the protein expression levels of MMP-2 and MMP-9. Pretreatment of RL95-2 cells with an ERK1/2 inhibitor (U0126) for 1h, followed by co-culture with Kisspeptin 234 (100nM) for 2h, attenuated the Kisspeptin 234-stimulated upregulation of MMP-2 and MMP-9 protein expression[5]. When mouse sperm were treated with Kisspeptin 234 (50μM) during the capacitation stage for 2h, followed by in vitro fertilization, a significant reduction in the fertilization rate was observed[6].
In vivo, co-injection of Kisspeptin 234 (1nM; 1.5μL) and Kisspeptin (1nM; 1.5μL) into the third cerebral ventricle of cannula-implanted Wistar rats significantly blocked the decrease in serum ghrelin levels induced by Kisspeptin alone[7]. Intrathecal administration of Kisspeptin 234 (1nM; 3μL) to CD1 mice 10min before formalin injection significantly reduced nociceptive behaviors (such as licking, lifting, and shaking of the injected paw) in both the first phase (0-10min) and the second phase (15-45min) of the formalin test[8].
References:
[1] LEI Z, BAI X, MA J, et al. Kisspeptin-13 inhibits bleomycin-induced pulmonary fibrosis through GPR54 in mice[J]. Molecular Medicine Reports, 2019, 20(2): 1049-1056.
[2] CHEN X, YANG S, SHAW N D, et al. Kisspeptin Receptor Agonists and Antagonists: Strategies for Discovery and Implications for Human Health and Disease[J]. International Journal of Molecular Sciences, 2025, 26(10): 4890.
[3] TENA-SEMPERE M. GPR54 and kisspeptin in reproduction[J]. Human Reproduction Update, 2006, 12(5): 631-639.
[4] DINH H, KOVÁCS Z Z A, KIS M, et al. Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy[J]. GeroScience, 2024, 46(2): 2463-2488.
[5] WU H M, CHEN L H, CHIU W J, et al. Kisspeptin Regulates Cell Invasion and Migration in Endometrial Cancer[J]. Journal of the Endocrine Society, 2024, 8(3): bvae001.
[6] HSU M C, WANG J Y, LEE Y J, et al. Kisspeptin modulates fertilization capacity of mouse spermatozoa[J]. Reproduction, 2014, 147(6): 835-845.
[7] SADEGHZADEH A, BAYRAMI A, MAHMOUDI F, et al. The effects of interaction of dopaminergic and kisspeptin neural pathways on ghrelin secretion in rats[J]. Journal of Paramedical Sciences, 2018, 9(1): 29-35.
[8] SPAMPINATO S, TRABUCCO A, BIASIOTTA A, et al. Hyperalgesic activity of kisspeptin in mice[J]. Molecular Pain, 2011, 7: 1744-8069-7-90.
Kisspeptin 234是一种由十个氨基酸组成的有效的Kisspeptin受体（KISS1/GPR54）拮抗剂[1]。Kisspeptin 234通过与GPR54结合抑制了kisspeptin对下丘脑-垂体-性腺（HPG）轴的刺激作用，减少了下丘脑促性腺激素释放激素（GnRH）的释放，进而抑制垂体随后释放黄体生成素（LH）[2]。Kisspeptin 234通常用于青春期启动、生殖疾病（如多囊卵巢综合征）和心血管疾病等领域的研究[3,4]。
在体外，Kisspeptin 234（100nM）处理4种人子宫内膜癌RL95-2、Ishikawa、HEC-1-A和HEC-1-B细胞系24h，显著促进了细胞的迁移能力。Kisspeptin 234（100nM）处理RL95-2细胞2h，显著提高了MMP-2和MMP-9的蛋白表达水平。使用ERK1/2抑制剂（U0126）预处理RL95-2细胞1h，再加入Kisspeptin 234（100nM）共同培养2h，削弱了由Kisspeptin 234刺激引起的MMP-2和MMP-9蛋白表达上调[5]。Kisspeptin 234（50μM）在精子获能阶段处理小鼠精子2h，随后进行体外受精，显著降低了精子的受精率[6]。
在体内，Kisspeptin 234（1nM; 1.5μL）和Kisspeptin（1nM; 1.5μL）共同注射到预植入套管的Wistar大鼠第三脑室中，显著阻断了单独注射Kisspeptin所引起的血清胃饥饿素（Ghrelin）水平下降[7]。Kisspeptin 234（1nM; 3μL）通过鞘内注射处理CD1小鼠10min，再注射福尔马林，能显著减少福尔马林测试第一时相（0-10min）和第二时相（15-45min）的伤害性行为（如舔爪、抬爪）[8]。