title: Receptor isoforms that mediate estrogen and progestagen action in the female lower urinary tract.
abstract: OBJECTIVE
  Bladder symptoms can be ameliorated by sex steroids but to our knowledge the mechanism of action is unknown. Previous studies of steroid receptor expression in the bladder did not indicate receptor subtype expression. We report the distribution of estrogen and progesterone receptor isoforms in the female lower urinary tract.
  
  
  METHODS
  Prospectively recruited women undergoing routine urogynecological or gynecological surgery provided cold cup biopsy samples from the bladder dome, trigone, and proximal and distal urethra. The samples were immediately frozen or fixed in formalin. After RNA extraction transcripts for estrogen receptor alpha and beta, and progesterone receptor A and B were noted on reverse transcriptase-polymerase chain reaction using isoform specific primers. The precise cellular localization of receptor proteins and their relative levels were assessed by immunochemistry in formalin fixed tissue sections with isoform specific antibodies.
  
  
  RESULTS
  Nine premenopausal and 10 postmenopausal women were recruited into the study. Two postmenopausal women on hormone replacement therapy. Estrogen receptor alpha and beta, and progesterone receptor A and B transcripts were detected in whole bladder extracts. Nuclear estrogen receptor alpha immunoreactivity was present in squamous epithelium but absent from transitional epithelium. Estrogen receptor beta immunoreactivity was expressed in squamous and transitional cell epithelium. Nuclear progesterone receptor expression was present in urethral squamous epithelium only. Progesterone receptor expression was greater in premenopausal women and in postmenopausal women on estrogen.
  
  
  CONCLUSIONS
  Estrogen receptor alpha and beta genes are transcribed in bladder tissue but only estrogen receptor beta is translated into protein, suggesting that the urothelium responds to endogenous estrogen via estrogen receptor beta. Progesterone receptor expression is confined to urethral squamous epithelium and the major isoform is progesterone receptor A.
authors.affiliation: Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Faculty of Medicine and Biological Sciences, University of Leicester, Leicester, United Kingdom.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Tincello
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Taylor
authors.forename: Susan M
authors.initials: SM
authors.lastname: Spurling
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bell
mesh_terms: D005260:Female; D006801:Humans; D017698:Postmenopause; D017697:Premenopause; D011446:Prospective Studies; D020033:Protein Isoforms; D011960:Receptors, Estrogen / Q000032:analysis* / Q000502:physiology*; D011980:Receptors, Progesterone / Q000032:analysis* / Q000502:physiology*; D014521:Urethra / Q000737:chemistry*; D001743:Urinary Bladder / Q000737:chemistry*
chemical_list: D020033:Protein Isoforms; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone