title: Chemerin-derived peptide C-20 suppressed gonadal steroidogenesis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Radioligand binding assay, receptor internalization assay, and early response gene C-FOS simulation, cAMP assay were carried out in chemokine-like receptor 1 (CMKLR1)/HEK293 transfectants and G protein-coupled receptor 1 (GPR1)/HEK293 transfectants. In vitro 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors: Lei
authors: L
authors: Li
authors: Chen
authors: C
authors: Huang
authors: Xu
authors: X
authors: Zhang
authors: Jiangbo
authors: J
authors: Wang
authors: Ping
authors: P
authors: Ma
authors: Yongjun
authors: Y
authors: Liu
authors: Tianxia
authors: T
authors: Xiao
authors: Brian A
authors: BA
authors: Zabel
authors: Jian V
authors: JV
authors: Zhang
mesh_terms: D002633:Chemotaxis; D020740:Chimerin Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007985:Leydig Cells; D008297:Male; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000502:physiology*; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: C102741:CMKLR1 protein, human; D020740:Chimerin Proteins; C504821:GPR1 protein, human; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C000592089:chemerin-derived peptide C-20; D013739:Testosterone; D011374:Progesterone; D000242:Cyclic AMP
keywords: Adipokine; chemerin; chemotaxis; progesterone; testosterone