NCBI Summary:
This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This gene is located in the chemokine receptor gene cluster region. Two alternatively spliced transcript variants are expressed by the gene. [provided by RefSeq]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Comment
Expression regulated by
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Ovarian localization
Theca
Comment
Zhou C, et al reported the ovarian expression of chemokines and their receptors.
Recent studies suggest involvement of the immune system, including leukocytes and cytokines/chemokines, in various ovarian functions such as ovulation. Using the RT-PCR method, we examined expression of various chemokines and their receptors in normal mouse ovaries. Among seventeen examined chemokines (17 CC types and two CXC types), expressions of CC types MCP-1 and RANTES, and CXC type IP-10 were detected at high levels, while most CC types expressed at variable or low levels. Only five chemokines were not detected in the ovary. We next examined expression of chemokine receptors. CCR1 and CCR2, which are the receptors for MCP-1 and RANTES, were also expressed at constitutively high levels while others were not detectable. We further showed that a significant part of expression of both detected chemokines and receptors originated from peripheral blood leukocytes (PBL) circulating in the ovary. However, ovarian tissue was the major contributor of expression. Constitutive expression of several chemokines and their receptors suggests frequent migrations/movements of leukocytes in the ovary, which may be involved in ovarian functions other than ovulation.
Follicle stages
Preovulatory
Comment
Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle Dahm-Kahler P, et al .
Ovulation constitutes an inflammatory-like process, with macrophages migrating into the follicle. This study evaluates the production of two macrophage-specific chemokines, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1a (MIP-1a), in the human follicle at ovulation. Blood samples, follicular fluids and follicular cells were collected during menstrual and IVF cycles. Levels of MCP-1 and MIP-1a were measured in follicular fluid, blood plasma and cultured media (granulosa, theca and granulosa-lutein cells [GLCs]). Cells were cultured with or without LH, FSH, interleukin (IL)-1a, IL-1b, tumour necrosis factor (TNF) a, progesterone or estradiol. The levels of MCP-1 were markedly higher in follicular fluid as compared with blood plasma in both menstrual and IVF cycles. The difference in MCP-1 levels between follicular fluid and plasma in menstrual cycles increased from the follicular phase (three-fold difference) to the late ovulatory phase (25-fold). Levels of MIP-1a were low in plasma and follicular fluid of both menstrual and IVF cycles. Theca cells from follicles of menstrual cycles secreted both MCP-1 and MIP-1a under basal conditions, and the secretion was increased by addition of IL-1b (MCP-1 and MIP-1a) and IL-1a (MCP-1). GLCs secreted MCP-1 under basal conditions and also MIP-1a after IL-1b stimulation. The macrophage-specific chemokine MCP-1 is highly expressed and is induced by IL-1 in the theca layer of the human follicle at ovulation.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Genetic variation in the mcp-1 gene promoter associated with the risk of polycystic ovary syndrome. Li L et al. (2015) Monocyte chemoattractant protein-1 (MCP-1) is a pivotal chemokine in the inflammatory response, which plays an important role in recruiting monocytes to sites of injury and infection. However, the exact mechanism of Mcp-1 associated with PCOS risk was unknown. In this study, we explored whether the Mcp-1 -2518G>A polymorphism increases the risk of PCOS. We performed a comparative study of -2518G>A polymorphism of the Mcp-1 gene with PCOS. In addition, luciferase reporter assay was performed to evaluate the Mcp-1 transcriptional activity. A strong association was observed between the -2518G>A polymorphism of Mcp-1 gene and PCOS (p-value = 0.016, odd ratio (OR) = 0.693). A p-value under 0.05 is considered statistically significant. The genotype and allelic frequencies were assumed to be in Hardy-Weinberg equilibrium (HWE). The luciferase assays in 2 cell lines showed that the Mcp-1 -2518G>A substitution can increase the expression of Mcp-1. MCP-1 levels in serum for PCOS group were significantly higher than those in serum for controls (p-value = 0.02). Furthermore, the patients carrying a genotype A/A had significantly increased levels of MCP-1 in serum compared with levels of the MCP-1 of the patients with genotypes G/G and G/A (p-value = 0.031). This is the first study on the genetic variation of the Mcp-1 gene and PCOS. This finding suggests that the Mcp-1 -2518G>A polymorphism is associated with PCOS risk by affecting transcriptional activity, leading to an increased expression level of Mcp-1.//////////////////