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 fem...

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Main Authors: Batjargal Lkhagvajav, Haruhiko Kanasaki, Tuvshintugs Tumurbaatar, Zhuoma Cairang, Aki Oride, Hiroe Okada, Satoru Kyo
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/ije/6698205
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author Batjargal Lkhagvajav
Haruhiko Kanasaki
Tuvshintugs Tumurbaatar
Zhuoma Cairang
Aki Oride
Hiroe Okada
Satoru Kyo
author_facet Batjargal Lkhagvajav
Haruhiko Kanasaki
Tuvshintugs Tumurbaatar
Zhuoma Cairang
Aki Oride
Hiroe Okada
Satoru Kyo
author_sort Batjargal Lkhagvajav
collection DOAJ
description 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.
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spelling doaj-art-e04cdf638bb34a0f926c75b1e7088b1b2025-08-20T02:57:57ZengWileyInternational Journal of Endocrinology1687-83452025-01-01202510.1155/ije/6698205Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell ModelsBatjargal Lkhagvajav0Haruhiko Kanasaki1Tuvshintugs Tumurbaatar2Zhuoma Cairang3Aki Oride4Hiroe Okada5Satoru Kyo6Department of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyNeurotensin (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.http://dx.doi.org/10.1155/ije/6698205
spellingShingle Batjargal Lkhagvajav
Haruhiko Kanasaki
Tuvshintugs Tumurbaatar
Zhuoma Cairang
Aki Oride
Hiroe Okada
Satoru Kyo
Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
International Journal of Endocrinology
title Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
title_full Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
title_fullStr Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
title_full_unstemmed Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
title_short Neurotensin Expression in the Posterior Hypothalamus Is Influenced by an Increase in Kisspeptin Levels: Insights From In Vivo Rat Models and Hypothalamic Cell Models
title_sort neurotensin expression in the posterior hypothalamus is influenced by an increase in kisspeptin levels insights from in vivo rat models and hypothalamic cell models
url http://dx.doi.org/10.1155/ije/6698205
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