Chen Ting, Wu Haiying, Chen Xiuli, Xie Rongrong, Wang Fengyun, Sun Hui, Chen Linqi
Department of Endocrinology, Genetics and Metabolism, Children's Hospital of Soochow University, Suzhou 215000 Jiangsu, People's Republic of China.
Diabetes Metab Syndr Obes. 2020 Dec 1;13:4681-4688. doi: 10.2147/DMSO.S279901. eCollection 2020.
The well-known tumor suppressor transcriptional factor 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 is involved in the metabolic control of puberty. The current study aimed to investigate the underlying signaling pathway, through which mediated the metabolic control of puberty.
We engineered the expression of and/or in GT1-7 cells to investigate the interaction between and system, and their impact on GnRH secretion.
Overexpression of stimulated, while inhibition of by pifithrin-α significantly suppressed the GnRH secretion and expression levels in response to kisspeptin stimulation in GT1-7 cells. Furthermore, overexpressed suppressed and expression levels and increased expression levels in GT1-7 cell lines. On the other hand, inhibition of by pifithrin-α upregulated and c-Myc levels and downregulated expression levels. Moreover, overexpression counteracted the effect of overexpression in and co-overexpression cells, whose GnRH secretion and GPR54 expression levels were not different from controls. Meanwhile, suppression counteracted the effect of pifithrin-α, and the GnRH secretion and expression levels are not different from controls in and co-suppression cells.
These data suggest that is a central mediator of GnRH secretion in hypothalamus, and this effect is at least partly through the pathway.
著名的肿瘤抑制转录因子被认为是协调青春期时间的功能相关且层次排列的基因网络的核心枢纽之一。我们之前的研究表明，该因子参与青春期的代谢控制。本研究旨在探究其介导青春期代谢控制的潜在信号通路。
设计、背景、参与者、干预措施及主要观察指标：我们在GT1-7细胞中构建该因子和/或其他相关因子的表达，以研究它们之间的相互作用及其对促性腺激素释放激素（GnRH）分泌的影响。
在GT1-7细胞中，该因子的过表达刺激了GnRH分泌，而用pifithrin-α抑制该因子则显著抑制了亲吻素刺激后的GnRH分泌及相关因子表达水平。此外，过表达该因子在GT1-7细胞系中抑制了其他相关因子的表达水平并增加了某些特定因子的表达水平。另一方面，用pifithrin-α抑制该因子会上调某些因子和c-Myc水平并下调特定因子的表达水平。而且，该因子过表达抵消了在共同过表达细胞中其他因子过表达的作用，这些细胞的GnRH分泌和GPR54表达水平与对照组无差异。同时，该因子的抑制抵消了pifithrin-α的作用，在共同抑制细胞中GnRH分泌和相关因子表达水平与对照组无差异。
这些数据表明，该因子是下丘脑GnRH分泌的核心调节因子，且这种作用至少部分是通过该特定信号通路实现的。
