title: Intermedin attenuates LPS-induced inflammation in the rat testis.
abstract: First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.
authors.affiliation: Research Center for Gene and Cell Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen City, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Wai-sum
authors.initials: WS
authors.lastname: O
authors.forename: Fai
authors.initials: F
authors.lastname: Tang
authors.forename: Jian V
authors.initials: JV
authors.lastname: Zhang
mesh_terms: D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009920:Orchitis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D058265:Receptors, Adrenomedullin / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D058265:Receptors, Adrenomedullin; D053607:Adrenomedullin; D013739:Testosterone; D006861:Hydrogen Peroxide