Chemerin‐Derived Peptide C‐20 Suppressed Gonadal Steroidogenesis. (12th October 2013)

• Record Type: Journal Article
• Authors: Li, Lei; Huang, Chen; Zhang, Xu; Wang, Jiangbo; Ma, Ping; Liu, Yongjun; Xiao, Tianxia; Zabel, Brian A.; Zhang, Jian V.
• Is Part Of: American journal of reproductive immunology. Volume 71:Number 3(2014:Mar.)
• Page Start: 265
• Page End: 277
• Publication Date: 2013-10-12
• Subjects: Human reproduction -- Immunological aspects -- Periodicals; 616.69206
• DOI: 10.1111/aji.12164
• Languages: English
• ISSNs: 1046-7408

Abstract

<abstract abstract-type="main" id="aji12164-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="aji12164-sec-0001" sec-type="section"> <title>Problem</title> <p>Chemerin is a novel chemo‐attractant and adipokine involved in leukocyte recruitment, inflammation, adipogenesis, lipid/carbohydrate metabolism, and reproduction. Based on the bioinformatic search for putative small peptides in the conserved region of pre‐pro‐chemerin, an evolutionary conserved region flanked by potential convertase cleavage sites was identified and we named it as C‐20. The binding capacity of C‐20 to chemerin receptors and its potential bioactivities were investigated in this study.</p> </sec> <sec id="aji12164-sec-0002" sec-type="section"> <title>Method of study</title> <p>Radioligand binding assay, receptor internalization assay, and early response gene <italic>C‐FOS</italic> simulation, cAMP assay were carried out in chemokine‐like receptor 1 (CMKLR1)/HEK293 transfectants and G protein‐coupled receptor 1 (GPR1)/HEK293 transfectants. <italic>In vitro</italic> transwell chemotaxis assay in CMKLR1/L1.2 transfectants, primary Leydig cell culture, and antral follicle culture was explored to investigate the bioactivity of C‐20.</p> </sec> <sec id="aji12164-sec-0003" sec-type="section"> <title>Results</title> <p>C‐20 bound to chemerin receptors CMKLR1 and GPR1 with high affinity triggered CMKLR1 internalization and stimulated subsequent signal C‐FOS expression and cAMP production. C‐20, such as chemerin, showed CMKLR1‐dependent chemotactic property. Furthermore, in primary Leydig cells and antral follicles, C‐20 showed similar but less potent suppressive effect on human chorionic gonadotropin‐stimulated testosterone production and progesterone production, compared with chemerin.</p> </sec> <sec id="aji12164-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The novel chemerin‐derived C‐20 peptide binds to chemerin receptors CMKLR1 and GPR1 and showed similar but less potent bioactivity in chemotaxis and the suppression of gonadal steroidogenesis, suggesting that after optimization, C‐20 is possible to be a useful experimental tool for the understanding of the biological functions of chemerin/CMKLR1 and chemerin/GPR1 signaling.</p> </sec> </abstract>