title: Urethral dysfunction in female mice with estrogen receptor β deficiency.
abstract: Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ(+/+)) and knockout (ERβ(-/-)) female mice were generated (aged 6-8 weeks, n = 6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography-mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ(+/+) group, the LPP and MUCP values of the ERβ(-/-) group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ(-/-) female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ(-/-) mice. This study is the first study to estimate protein expression changes in urethras from ERβ(-/-) female mice. These changes could be related to the molecular mechanism of ERβ in SUI.
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Urology, George H Whipple Laboratory for Cancer Research, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Lin
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Tsong
authors.initials: WT
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Bor-Tsang
authors.initials: BT
authors.lastname: Wu
authors.affiliation: Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wen-Lung
authors.initials: WL
authors.lastname: Ma
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Urology, George H Whipple Laboratory for Cancer Research, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Huey-Yi
authors.initials: HY
authors.lastname: Chen
mesh_terms: D000818:Animals; D015536:Down-Regulation; D047629:Estrogen Receptor beta / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D005838:Genotype; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011312:Pressure; D011506:Proteins / Q000378:metabolism; D040901:Proteomics; D015854:Up-Regulation; D014521:Urethra / Q000378:metabolism* / Q000503:physiopathology*; D014563:Urodynamics
chemical_list: D047629:Estrogen Receptor beta; D011506:Proteins