Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models

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.