Monocyte Chemoattractant Protein-1 stimulates the differentiation of rat stem and progenitor Leydig cells during regener
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RESEARCH ARTICLE
Open Access
Monocyte Chemoattractant Protein-1 stimulates the differentiation of rat stem and progenitor Leydig cells during regeneration Xiangcheng Zhan1,2, Jingwei Zhang3, Saiyang Li1,4, Xiaolu Zhang1, Linchao Li5, Tiantian Song5, Qunlong Liu1,4, Jun Lu1,5, Yunfei Xu1,2,4* and Ren-Shan Ge5*
Abstract Background: Monocyte chemoattractant protein-1(MCP-1) is a chemokine secreted by Leydig cells and peritubular myoid cells in the rat testis. Its role in regulating the development of Leydig cells via autocrine and paracrine is still unclear. The objective of the current study was to investigate the effects of MCP-1 on Leydig cell regeneration from stem cells in vivo and on Leydig cell development in vitro. Results: Intratesticular injection of MCP-1(10 ng/testis) into Leydig cell-depleted rat testis from post-EDS day 14 to 28 significantly increased serum testosterone and luteinizing hormone levels, up-regulated the expression of Leydig cell proteins, LHCGR, SCARB1, CYP11A1, HSD3B1, CYP17A1, and HSD17B3 without affecting progenitor Leydig cell proliferation, as well as increased ERK1/2 phosphorylation. MCP-1 (100 ng/ml) significantly increased medium testosterone levels and up-regulated LHCGR, CYP11A1, and HSD3B1 expression without affecting EdU incorporation into stem cells after in vitro culture for 7 days. RS102895, a CCR2 inhibitor, reversed MCP-1-mediated increase of testosterone level after culture in combination with MCP-1. Conclusion: MCP-1 stimulates the differentiation of stem and progenitor Leydig cells without affecting their proliferation. Keywords: Monocyte chemoattractant protein-1, Stem Leydig cells, Proliferation, Differentiation, Testosterone
Background Testosterone is critical for maintaining the secondary sexual characteristics and promoting spermatogenesis in adult males [1]. Approximately 95% of circulatory testosterone amount is contributed by the Leydig cells, which are located in the interstitium of the adult testis. To maintain the normal testosterone production, certain numbers of * Correspondence: [email protected]; [email protected] 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China 5 Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China Full list of author information is available at the end of the article
Leydig cells and the full-scale capacity of steroidogenesis per se are required by each testis. These properties of Leydig cells are achieved via their pubertal development. Although pituitary luteinizing hormone (LH) is important for maintaining the full capacity of androgen production and the late-stage development of Leydig cells after it binds its receptor (LHCGR), many other growth factors and cytokines are also involved [1]. However, the regulation of Leydig cell development by these growth factors and cytokines is not well investigated. Our research group previously isolated and identified a
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