p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells

Ting Chen, Haiying Wu, Xiuli Chen, Rongrong Xie, Fengyun Wang, Hui Sun, Linqi Chen Department of Endocrinology, Genetics and Metabolism, Children’s Hospital of Soochow University, Suzhou 215000 Jiangsu, People’s Republic of ChinaCorrespondence: Ting ChenDepartment of Endocrinolog...

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Autores principales:	Chen T, Wu H, Chen X, Xie R, Wang F, Sun H, Chen L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	pubertal timing p53 lin28/let-7 system gonadotropin-releasing hormone Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/f2be1995a7e540118347993de12a88ca
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spelling	oai:doaj.org-article:f2be1995a7e540118347993de12a88ca2021-12-02T13:02:00Zp53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells1178-7007https://doaj.org/article/f2be1995a7e540118347993de12a88ca2020-12-01T00:00:00Zhttps://www.dovepress.com/p53-mediates-gnrh-secretion-via-lin28let-7-system-in-gt1-7-cells-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Ting Chen, Haiying Wu, Xiuli Chen, Rongrong Xie, Fengyun Wang, Hui Sun, Linqi Chen Department of Endocrinology, Genetics and Metabolism, Children’s Hospital of Soochow University, Suzhou 215000 Jiangsu, People’s Republic of ChinaCorrespondence: Ting ChenDepartment of Endocrinology, Genetics, and Metabolism, Children’s Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of ChinaTel +86-512-8069-8322Email chenting888@suda.edu.cnStudy Objective: The well-known tumor suppressor transcriptional factor p53 has been proposed to be one of the central hubs of a functionally related and hierarchically arranged gene network coordinating pubertal timing. Our previous studies revealed that p53 is involved in the metabolic control of puberty. The current study aimed to investigate the underlying signaling pathway, through which p53 mediated the metabolic control of puberty.Design, Setting, Participants, Interventions, and Main Outcome Measures: We engineered the expression of p53 and/or Lin28a in GT1-7 cells to investigate the interaction between p53 and Lin28/let-7 system, and their impact on GnRH secretion.Results: Overexpression of p53 stimulated, while inhibition of p53 by pifithrin-α significantly suppressed the GnRH secretion and GPR54 expression levels in response to kisspeptin stimulation in GT1-7 cells. Furthermore, overexpressed p53 suppressed Lin28a and c-Myc expression levels and increased let-7 expression levels in GT1-7 cell lines. On the other hand, inhibition of p53 by pifithrin-α upregulated Lin28a and c-Myc levels and downregulated let-7 expression levels. Moreover, Lin28a overexpression counteracted the effect of p53 overexpression in p53 and Lin28a co-overexpression cells, whose GnRH secretion and GPR54 expression levels were not different from controls. Meanwhile, Lin28a suppression counteracted the effect of pifithrin-α, and the GnRH secretion and GPR54 expression levels are not different from controls in p53 and Lin28a co-suppression cells.Conclusion: These data suggest that p53 is a central mediator of GnRH secretion in hypothalamus, and this effect is at least partly through the Lin28/let-7 pathway.Keywords: pubertal timing, p53, Lin28/let-7 system, gonadotropin-releasing hormoneChen TWu HChen XXie RWang FSun HChen LDove Medical Pressarticlepubertal timingp53lin28/let-7 systemgonadotropin-releasing hormoneSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4681-4688 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	pubertal timing p53 lin28/let-7 system gonadotropin-releasing hormone Specialties of internal medicine RC581-951
spellingShingle	pubertal timing p53 lin28/let-7 system gonadotropin-releasing hormone Specialties of internal medicine RC581-951 Chen T Wu H Chen X Xie R Wang F Sun H Chen L p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
description	Ting Chen, Haiying Wu, Xiuli Chen, Rongrong Xie, Fengyun Wang, Hui Sun, Linqi Chen Department of Endocrinology, Genetics and Metabolism, Children’s Hospital of Soochow University, Suzhou 215000 Jiangsu, People’s Republic of ChinaCorrespondence: Ting ChenDepartment of Endocrinology, Genetics, and Metabolism, Children’s Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of ChinaTel +86-512-8069-8322Email chenting888@suda.edu.cnStudy Objective: The well-known tumor suppressor transcriptional factor p53 has been proposed to be one of the central hubs of a functionally related and hierarchically arranged gene network coordinating pubertal timing. Our previous studies revealed that p53 is involved in the metabolic control of puberty. The current study aimed to investigate the underlying signaling pathway, through which p53 mediated the metabolic control of puberty.Design, Setting, Participants, Interventions, and Main Outcome Measures: We engineered the expression of p53 and/or Lin28a in GT1-7 cells to investigate the interaction between p53 and Lin28/let-7 system, and their impact on GnRH secretion.Results: Overexpression of p53 stimulated, while inhibition of p53 by pifithrin-α significantly suppressed the GnRH secretion and GPR54 expression levels in response to kisspeptin stimulation in GT1-7 cells. Furthermore, overexpressed p53 suppressed Lin28a and c-Myc expression levels and increased let-7 expression levels in GT1-7 cell lines. On the other hand, inhibition of p53 by pifithrin-α upregulated Lin28a and c-Myc levels and downregulated let-7 expression levels. Moreover, Lin28a overexpression counteracted the effect of p53 overexpression in p53 and Lin28a co-overexpression cells, whose GnRH secretion and GPR54 expression levels were not different from controls. Meanwhile, Lin28a suppression counteracted the effect of pifithrin-α, and the GnRH secretion and GPR54 expression levels are not different from controls in p53 and Lin28a co-suppression cells.Conclusion: These data suggest that p53 is a central mediator of GnRH secretion in hypothalamus, and this effect is at least partly through the Lin28/let-7 pathway.Keywords: pubertal timing, p53, Lin28/let-7 system, gonadotropin-releasing hormone
format	article
author	Chen T Wu H Chen X Xie R Wang F Sun H Chen L
author_facet	Chen T Wu H Chen X Xie R Wang F Sun H Chen L
author_sort	Chen T
title	p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
title_short	p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
title_full	p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
title_fullStr	p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
title_full_unstemmed	p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
title_sort	p53 mediates gnrh secretion via lin28/let-7 system in gt1-7 cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/f2be1995a7e540118347993de12a88ca
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p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells

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