Effects of the Fertility Drugs Clomiphene Citrate and Letrozole on Kiss-1 Expression in Hypothalamic Kiss-1-Expressing Cell Models
Effects of the Fertility Drugs Clomiphene Citrate and Letrozole on Kiss-1 Expression in Hypothalamic Kiss-1-Expressing Cell Models
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生育药物克罗米芬柠檬酸盐和来曲唑对下丘脑 Kiss-1 表达细胞模型中 Kiss-1 表达的影响
DOI：
10.1007/s43032-020-00154-1
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kyo S
中科院分区：
文献类型：
--
作者：
Oride A;Kanasaki H;Tumurbaatar T;Tumurgan Z;Okada H;Kyo S
克罗米芬（CC）和来曲唑刺激下丘脑-垂体-卵巢轴，并被广泛用作诱导卵泡生成的口服生育药物。我们研究了这些药物是否增加下丘脑细胞模型中Kiss-1的表达。我们利用了两个下丘脑细胞模型，mHypoA-50和mHypoA-55，分别起源于小鼠下丘脑前腹侧室周核（AVPV）和弓状核（ARC）中的Kiss-1神经元。用CC或来曲唑刺激细胞，之后测定Kiss-1 mRNA表达。CC刺激mHypoA-50和mHypoA-55细胞中Kiss-1基因的表达。在mHypoA-50细胞中，雌二醇（E2）存在下Kiss-1的基础表达显著增加，在这些细胞中，在E2存在下未观察到CC诱导的Kiss-1表达增加。与此相反，E2并没有修改mHypoA-55细胞Kiss-1的基础表达，CC诱导的Kiss-1的表达在E2的存在下仍然可以观察到。在雌激素受体拮抗剂的存在下，mHypoA-50和mHypoA-55细胞中Kiss-1基因表达的显著增加被钝化。芳香化酶在mHypoA-50和mHypoA-55细胞中表达。芳香化酶抑制剂来曲唑增加mHypoA-55 ARC细胞中Kiss-1的表达，但在mHypoA-50 AVPV细胞中不增加。虽然Kiss-1的基础表达增加E2，来曲唑并没有调节Kiss-1在mHypoA-50细胞中的表达。来曲唑诱导的Kiss-1基因在mHypoA-55细胞中的表达在E2的存在下不受调节。生育药物CC和来曲唑调节下丘脑细胞模型中Kiss-1的表达。
Clomiphene citrate (CC) and letrozole stimulate the hypothalamic-pituitary-ovarian axis and are used widely as oral fertility drugs to induce folliculogenesis. We examined whether these drugs increase Kiss-1 expression in hypothalamic cell models. We utilized two hypothalamic cell models, mHypoA-50 and mHypoA-55, which originated from Kiss-1 neurons in the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus of the mouse hypothalamus, respectively. The cells were stimulated with CC or letrozole, after which Kiss-1 mRNA expression was determined. CC stimulated Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells. The basal expression of Kiss-1 was significantly increased in the presence of estradiol (E2) in mHypoA-50 cells, and the CC-induced increase in Kiss-1 expression was not observed in the presence of E2 in these cells. In contrast, E2 did not modify the basal expression of Kiss-1 in mHypoA-55 cells, and CC-induced Kiss-1 expression was still observed in the presence of E2. The significant increase in Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells was blunted in the presence of estrogen receptor antagonists. Aromatase was expressed in mHypoA-50 and mHypoA-55 cells. Letrozole, an aromatase inhibitor, increased Kiss-1 expression in mHypoA-55 ARC cells but not in mHypoA-50 AVPV cells. Although the basal expression of Kiss-1 was increased by E2, letrozole did not modulate Kiss-1 expression in mHypoA-50 cells. Letrozole-induced Kiss-1 gene expression in mHypoA-55 cells was not modulated in the presence of E2. The fertility drugs CC and letrozole modulated Kiss-1 expression in hypothalamic cell models.