Lkhagvajav Batjargal, Kanasaki Haruhiko, Tumurbaatar Tuvshintugs, Cairang Zhuoma, Oride Aki, Okada Hiroe, Kyo Satoru
Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.
Int J Endocrinol. 2025 Jul 31;2025:6698205. doi: 10.1155/ije/6698205. eCollection 2025.
Neurotensin (NT) is a hypothalamic peptide that acts as a neurohormone and exerts a potent vascular effect. NT is also implicated in regulating the reproductive system. In the present study, we examined the role of NT in the hypothalamic-pituitary-gonadal axis using rat and cell-based models. In female rats, NT gene expression within the posterior part of the hypothalamus was increased by 1.53 ± 0.2-fold by ovariectomy (OVX), and this increase was prevented by estradiol (E2) supplementation after OVX. E2 administration to ovary-intact rats reduced NT gene expression in this part of the hypothalamus. Progesterone (P4) and dihydrotestosterone (DHT) administration also prevented the OVX-induced increase of NT gene expression, while P4 and DHT administration to ovary-intact rats reduced hypothalamic NT gene expression. As previously reported, Kiss-1 gene expression in the posterior part of the hypothalamus was increased by OVX, and this increase was repressed by sex steroid supplementation after OVX. In experiments using hypothalamic cell models, E2 slightly increased NT mRNA expression by 1.67 ± 0.19-fold in GT1-7 cells but failed to increase its expression in rHypoE-8 cells. E2 stimulation slightly increased Kiss-1 gene expression in GT1-7 and rHypoE8 hypothalamic cells by 1.45 ± 0.03-fold and 1.57 ± 0.25-fold, respectively. NT stimulation failed to increase Kiss-1 gene expression in GT1-7 cells but increased its expression significantly in rHypoE8 cells by 1.96 ± 0.22-fold. In contrast, kisspeptin significantly increased NT mRNA expression in GT1-7 (1.85 ± 0.18-fold) and rHypoE8 (4.41 ± 1.03-fold) cells. In the mHypoA-55 hypothalamic KNDy neuron cell model, kisspeptin also significantly increased NT gene expression by 2.13 ± 0.28-fold. Although E2 had some effect on NT expression in hypothalamic cells, kisspeptin significantly increased NT gene expression in three different hypothalamic cell lines. Given that the NT and Kiss-1 gene expression patterns in OVX rats and the effects of sex steroid supplementation were similar, the OVX-induced increase in NT gene expression in the hypothalamus might depend on the increase in Kiss-1/kisspeptin expression within this part of the hypothalamus.
神经降压素（NT）是一种下丘脑肽，作为神经激素发挥作用，并具有强大的血管效应。NT也参与调节生殖系统。在本研究中，我们使用大鼠和细胞模型研究了NT在下丘脑-垂体-性腺轴中的作用。在雌性大鼠中，卵巢切除（OVX）使下丘脑后部的NT基因表达增加了1.53±0.2倍，而OVX后补充雌二醇（E2）可防止这种增加。对卵巢完整的大鼠施用E2可降低下丘脑这一部分的NT基因表达。施用孕酮（P4）和双氢睾酮（DHT）也可防止OVX诱导的NT基因表达增加，而对卵巢完整的大鼠施用P4和DHT可降低下丘脑NT基因表达。如先前报道，OVX使下丘脑后部的Kiss-1基因表达增加，而OVX后补充性类固醇可抑制这种增加。在使用下丘脑细胞模型的实验中，E2使GT1-7细胞中的NT mRNA表达略有增加，为1.67±0.19倍，但未能增加rHypoE-8细胞中的表达。E2刺激使GT1-7和rHypoE8下丘脑细胞中的Kiss-1基因表达分别略有增加，为1.45±0.03倍和1.57±0.25倍。NT刺激未能增加GT1-7细胞中的Kiss-1基因表达，但使rHypoE8细胞中的表达显著增加，为1.96±0.22倍。相反，亲吻素使GT1-7（1.85±0.18倍）和rHypoE8（4.41±1.03倍）细胞中的NT mRNA表达显著增加。在mHypoA-55下丘脑KNDy神经元细胞模型中，亲吻素也使NT基因表达显著增加，为2.13±0.28倍。尽管E2对下丘脑细胞中的NT表达有一些影响，但亲吻素在三种不同的下丘脑细胞系中显著增加了NT基因表达。鉴于OVX大鼠中NT和Kiss-1基因表达模式以及性类固醇补充的影响相似，OVX诱导的下丘脑NT基因表达增加可能取决于下丘脑这一部分中Kiss-1/亲吻素表达的增加。
