The potential regulatory mechanisms of the gonadotropin-releasing hormone in gonadotropin transcriptions identified with bioinformatics analyses

文献类型： 外文期刊

第一作者： Xiang, Wei

作者： Xiang, Wei;Zhang, Baoyun;Lv, Fenglin;Chen, Long;Yang, Fang;Zhang, Ke;Cao, Chunyu;Wang, Pingqing;Feng, Guangde;Chu, Mingxing

作者机构：

关键词： Molecular mechanisms;GnRH signalling pathway;Bioinformatics analyses;Metabolic status

期刊名称：REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY （ 影响因子：5.211； 五年影响因子：5.017 ）

ISSN： 1477-7827

年卷期： 2017 年 15 卷

页码：

收录情况： SCI

摘要： Background: The regulation of gonadotropin synthesis and release by gonadotropinreleasing hormone (GnRH) plays an essential role in the neuroendocrine control of reproduction. However, the mechanisms underlying gonadotropin regulation by GnRH pulse frequency and amplitude are still ambiguous. This study aimed to explore the molecular mechanisms and biological pathways associated with gonadotropin synthesis by GnRH pulse frequencies and amplitudes. Methods: Using GSE63251 datasets downloaded from the Gene Expression Omnibus (GEO), differentially expressed genes (DEGs) were screened by comparing the RNA expression from the GnRH pulse group, the GnRH tonic group and the control group. Pathway enrichment analyses of DEGs was performed, followed by protein-protein interaction (PPI) network construction. Furthermore, sub-network modules were constructed by ClusterONE and GO function and pathways analysed by DAVID. In addition, the relationship between the metabolic pathways and the GnRH pathway was verified in vitro. Results: In total, 531 common DEGs were identified in GnRH groups, including 290 up-regulated and 241 down-regulated genes. DEGs predominantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including 11 up-regulated pathways (signallingsignalling metabolic pathways, signallingand GnRH signalling pathway) and 5 down-regulated pathways (type II diabetes mellitus). Moreover, FBJ osteosarcoma oncogene (FOS) and jun proto-oncogene (JUN) had higher connectivity degrees in the PPI network. Three modules in the PPI were identified with ClusterONE. The genes in module 1 were significantly enriched in five pathways, including signalling the insulin resistance and GnRH signalling pathway. The genes in modules 2 and 3 were mainly enriched in metabolic pathways and steroid hormone biosynthesis, respectively. Finally, knockdown leptin receptor (LEPR) and insulin receptor (INSR) reversed the GnRH-modulated metabolic related-gene expression. Conclusions: The present study revealed the involvement of GnRH in the regulation of gonadotropin biosynthesis and metabolism in the maintenance of reproduction, achieved by bioinformatics analyses. This, indicates that the GnRH signalling pathway played a central linkings role in reproductive function and metabolic balance. In addition, the present study identified the difference response between GnRH pulse and GnRH tone, indicated that abnormal GnRH pulse and amplitude may cause disease, which may provide an improved understanding of the GnRH pathway and a new insight for disease diagnosis and treatment.

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