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- Title
p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells.
- Authors
Chen, Ting; Wu, Haiying; Chen, Xiuli; Xie, Rongrong; Wang, Fengyun; Sun, Hui; Chen, Linqi
- Abstract
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.
- Subjects
SECRETION; METABOLIC regulation; CELLS; CELL lines; HYPOTHALAMUS
- Publication
Diabetes, Metabolic Syndrome & Obesity: Targets & Therapy, 2020, Vol 13, p4681
- ISSN
1178-7007
- Publication type
Article
- DOI
10.2147/DMSO.S279901