Abstract
BackgroundMonocyte 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.ResultsIntratesticular 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.ConclusionMCP-1 stimulates the differentiation of stem and progenitor Leydig cells without affecting their proliferation.
Highlights
Monocyte chemoattractant protein-1(MCP-1) is a chemokine secreted by Leydig cells and peritubular myoid cells in the rat testis
MCP-1 significantly increased serum testosterone levels at 10 ng/testis (Fig. 1b) and luteinizing hormone (LH) levels at 1 and 10 ng/ testis (Fig. 1c). It did not alter serum FSH levels (Fig. 1d). These results indicate that MCP-1 promotes Leydig cell regeneration process
MCP-1 is constitutively expressed in peritubular myoid cells [6] as well as stem Leydig cells and MCP-1 promoted Leydig cell regeneration by inducing their differentiation, as evidence of the facts that MCP-1 increased the expression of Leydig cell specific genes, such as Lhcgr, Scavenger receptor class B type I (Scarb1), Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 and their proteins (LHCGR, SCARB1, Cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A1), HSD3B1, Cytochrome P450 17α-hydroxylase (CYP17A1), and HSD17B3) as well as increased serum testosterone levels in ethane dimethane sulfonate (EDS)-treated Leydig cell regeneration model in rats
Summary
Monocyte chemoattractant protein-1(MCP-1) is a chemokine secreted by Leydig cells and peritubular myoid cells in the rat testis. To maintain the normal testosterone production, certain numbers of 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. 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 involved [1]. The regulation of Leydig cell development by these growth factors and cytokines is not well investigated. Our research group previously isolated and identified a platelet-derived growth factor receptor α (PDGFRA)-positive stem Leydig cell, which is capable of committing into the Leydig cell lineage
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