title: Androgenic regulation of beta-defensins in the mouse epididymis.
abstract: BACKGROUND
  The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins.
  
  
  METHODS
  The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR.
  
  
  RESULTS
  We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens.
  
  
  CONCLUSIONS
  The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility.
authors.forename: Shuang-Gang
authors.initials: SG
authors.lastname: Hu
authors.forename: Mei
authors.initials: M
authors.lastname: Zou
authors.forename: Guang-Xin
authors.initials: GX
authors.lastname: Yao
authors.forename: Wu-Bin
authors.initials: WB
authors.lastname: Ma
authors.forename: Qin-Ling
authors.initials: QL
authors.lastname: Zhu
authors.forename: Xiang-Qi
authors.initials: XQ
authors.lastname: Li
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China. syun163@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000728:Androgens / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002369:Castration; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004822:Epididymis / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007438:Introns / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects; D043343:Testosterone Propionate / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D023083:beta-Defensins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000728:Androgens; D020033:Protein Isoforms; D011944:Receptors, Androgen; D023083:beta-Defensins; D043343:Testosterone Propionate
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