title: The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice.
abstract: BACKGROUND
  Successful reproductive efforts require the establishment of a situation favorable for reproduction that requires integration of both behavior and internal physiological events. TR4 nuclear receptor is known to be involved in male fertility via controlling spermatogenesis, yet its roles in regulating other biological events related to reproduction have not been completely revealed.
  
  
  METHODS
  Male TR4 knockout (TR4 -/-) and wild type mice were used for the sexual behavior and penile dysfunction studies. Mice were sacrificed for histological examination and corresponding genes profiles were analyzed by quantitative RT-PCR. Reporter gene assays were performed.
  
  
  RESULTS
  We describe an unexpected finding of priapism in TR4 -/- mice. As a transcriptional factor, we demonstrated that TR4 transcriptionally modulates a key enzyme regulating penis erection and neuronal nitric oxide synthese NOS (nNOS). Thereby, elimination of TR4 results in nNOS reduction in both mRNA and protein levels, consequently may lead to erectile dysfunction. In addition, male TR4 -/- mice display defects in sexual and social behavior, with increased fear or anxiety, as well as reduced mounting, intromission, and ejaculation. Reduction of ER alpha, ER beta, and oxytocin in the hypothalamus may contribute to defects in sexual behavior and stress response.
  
  
  CONCLUSIONS
  Together, these results provide in vivo evidence of important TR4 roles in penile physiology, as well as in male sexual behavior. In conjunction with previous finding, TR4 represents a key factor that controls male fertility via regulating behavior and internal physiological events.
authors: George Whipple Lab for Cancer Research, Department of Pathology, The Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors: Loretta L
authors: LL
authors: Collins
authors: Yi-Fen
authors: YF
authors: Lee
authors: Huei-Ju
authors: HJ
authors: Ting
authors: Wen-Jye
authors: WJ
authors: Lin
authors: Ning-Chun
authors: NC
authors: Liu
authors: Charles K
authors: CK
authors: Meshul
authors: Hideo
authors: H
authors: Uno
authors: Bo-Ying
authors: BY
authors: Bao
authors: Yen-Ta
authors: YT
authors: Chen
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005298:Fertility; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000235:genetics / Q000502:physiology*; D010413:Penis / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011317:Priapism / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020218:Response Elements; D012720:Severity of Illness Index; D012726:Sexual Behavior, Animal; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse