Functions of estradiol in the urinary bladder

Whether estrogens have beneficial effects in the urinary bladder to prevent occurrence of urinary bladder incontinence is an open question. Effects of E2 have been studied in vitro using urinary bladder strips but not in vivo in animal models. Therefore, we studied the chronically ovariectomized (ovx) rat kept under estradiol (E2) (daily dose 0.1, 1.0, and 10µg s.c. for 4 weeks). To test receptor specificity the intermediate dose was used with the E2 antagonist ZM182780 2.5mg. Four weeks after ovx a urinary bladder catheter was inserted in isoflurane-anaesthetized Sprague Dawley rats. Within 2×30s (1min apart) 0.5ml NaCl 0.9% solution was infused into the bladder and the vesicular pressure recorded. Lowest urinary bladder pressures were recorded in the sham-treated control animals. The lowest dose of E2, resulting in diestrous serum E2 concentrations, caused an increase in urinary bladder pressure during the first (p<0.05) but not during the second filling period. The intermediate dose, resulting in slightly supraphysiological serum E2 levels, yielded a dramatic increase in urinary bladder pressure during both filling periods (p<0.05). Surprisingly, the highest dose had no significant effect on urinary bladder pressure. The effects of the intermediate dose of E2 were totally abolished by co-administration of the antiestrogen ZM182780. Immunocytochemically we demonstrated that the urothelium stains positively for the estrogen receptor of the β-subtype (ERβ) whereas the ERα protein was primarily found in the interstitial fibroblasts and myocytes of the detrusor muscle. It is concluded that estrogen deprivation causes significant reduction of the reactivity of the urinary bladder to filling conditions which could be prevented by E2 resulting in physiologic but not pharmacologic serum E2 levels. These effects may be exerted either through ERα and/or ERβ which were demonstrable in the cellular compounds of the urinary bladder.