Receptor Isoforms That Mediate Estrogen and Progestagen Action in the Female Lower Urinary Tract

Purpose: 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. Materials and 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 a 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.