Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice

In recent years, the age of children entering puberty is getting lower and the incidence of central precocious puberty is increasing. It is known that melatonin plays an increasingly important role in regulating animal reproduction, but the specific role and mechanism of melatonin in regulating the...

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Main Authors: Zixuan Chen, Lina Si, Weihan Shu, Xin Zhang, Chenyang Wei, Meng Wei, Luyang Cheng, Zhihong Chen, Yuebing Qiao, Songhe Yang
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/11/1550
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author Zixuan Chen
Lina Si
Weihan Shu
Xin Zhang
Chenyang Wei
Meng Wei
Luyang Cheng
Zhihong Chen
Yuebing Qiao
Songhe Yang
author_facet Zixuan Chen
Lina Si
Weihan Shu
Xin Zhang
Chenyang Wei
Meng Wei
Luyang Cheng
Zhihong Chen
Yuebing Qiao
Songhe Yang
author_sort Zixuan Chen
collection DOAJ
description In recent years, the age of children entering puberty is getting lower and the incidence of central precocious puberty is increasing. It is known that melatonin plays an increasingly important role in regulating animal reproduction, but the specific role and mechanism of melatonin in regulating the initiation of puberty remain unclear. The purpose of the current study was to investigate the effect of subcutaneous melatonin injection on pubertal development in female mice and its mechanism of action. Female mice that were 22 days old received 1 mg/kg doses of melatonin subcutaneously every day for 10, 15 and 20 days. The vaginal opening was checked daily. Hematoxylin and eosin (HE) stain was used to determine the growth of the uterus and ovaries. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of follicle-stimulating hormone (FSH), gonadotropin-inhibiting hormone (GnIH), and gonadotropin-releasing hormone (GnRH) in serum. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus GnRH, GnIH, Kisspeptin (Kp), Proopiomelanocortin (POMC), Neuropeptide Y (NPY), as well as G protein-coupled receptor 147 (GPR147) were identified. The findings demonstrated that melatonin could suppress ovarian follicle and uterine wall growth as well as delay vaginal opening, decrease serum levels of GnRH and FSH and increase levels of GnIH. Melatonin increased GnIH and GPR147 expression in the hypothalamus in comparison to the saline group, while decreasing the expression of GnRH, Kisspeptin, POMC, and NPY. In conclusion, exogenous melatonin can inhibit the onset of puberty in female mice by modulating the expression of hypothalamic GnRH, GnIH, Kisspeptin, POMC and NPY neurons and suppressing the hypothalamic–pituitary–gonadal axis.
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spelling doaj.art-a5a1329591a24f98a73f64699207d08a2023-11-24T07:49:37ZengMDPI AGBrain Sciences2076-34252022-11-011211155010.3390/brainsci12111550Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female MiceZixuan Chen0Lina Si1Weihan Shu2Xin Zhang3Chenyang Wei4Meng Wei5Luyang Cheng6Zhihong Chen7Yuebing Qiao8Songhe Yang9Department of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaDepartment of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaDepartment of Immunology, Chengde Medical University, Chengde 067000, ChinaDepartment of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaDepartment of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaDepartment of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaDepartment of Immunology, Chengde Medical University, Chengde 067000, ChinaFaculty of Graduate Studies, Chengde Medical University, Chengde 067000, ChinaDepartment of Human Anatomy, Chengde Medical University, Chengde 067000, ChinaFaculty of Graduate Studies, Chengde Medical University, Chengde 067000, ChinaIn recent years, the age of children entering puberty is getting lower and the incidence of central precocious puberty is increasing. It is known that melatonin plays an increasingly important role in regulating animal reproduction, but the specific role and mechanism of melatonin in regulating the initiation of puberty remain unclear. The purpose of the current study was to investigate the effect of subcutaneous melatonin injection on pubertal development in female mice and its mechanism of action. Female mice that were 22 days old received 1 mg/kg doses of melatonin subcutaneously every day for 10, 15 and 20 days. The vaginal opening was checked daily. Hematoxylin and eosin (HE) stain was used to determine the growth of the uterus and ovaries. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of follicle-stimulating hormone (FSH), gonadotropin-inhibiting hormone (GnIH), and gonadotropin-releasing hormone (GnRH) in serum. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus GnRH, GnIH, Kisspeptin (Kp), Proopiomelanocortin (POMC), Neuropeptide Y (NPY), as well as G protein-coupled receptor 147 (GPR147) were identified. The findings demonstrated that melatonin could suppress ovarian follicle and uterine wall growth as well as delay vaginal opening, decrease serum levels of GnRH and FSH and increase levels of GnIH. Melatonin increased GnIH and GPR147 expression in the hypothalamus in comparison to the saline group, while decreasing the expression of GnRH, Kisspeptin, POMC, and NPY. In conclusion, exogenous melatonin can inhibit the onset of puberty in female mice by modulating the expression of hypothalamic GnRH, GnIH, Kisspeptin, POMC and NPY neurons and suppressing the hypothalamic–pituitary–gonadal axis.https://www.mdpi.com/2076-3425/12/11/1550melatoninpubertyGnRHGnIHKisspeptinNeuropeptide Y
spellingShingle Zixuan Chen
Lina Si
Weihan Shu
Xin Zhang
Chenyang Wei
Meng Wei
Luyang Cheng
Zhihong Chen
Yuebing Qiao
Songhe Yang
Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
Brain Sciences
melatonin
puberty
GnRH
GnIH
Kisspeptin
Neuropeptide Y
title Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
title_full Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
title_fullStr Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
title_full_unstemmed Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
title_short Exogenous Melatonin Regulates Puberty and the Hypothalamic GnRH-GnIH System in Female Mice
title_sort exogenous melatonin regulates puberty and the hypothalamic gnrh gnih system in female mice
topic melatonin
puberty
GnRH
GnIH
Kisspeptin
Neuropeptide Y
url https://www.mdpi.com/2076-3425/12/11/1550
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