A dose-dependent dual effect of oestrogen on voiding in the male mouse?


Tomi Streng, Department of Clinical and Experimental Pharmacology, Lund University Hospital, SE-221 85 Lund, Sweden.
e-mail: tomi.streng@med.lu.se



To explore the effect of different degrees of oestrogenization on male voiding, by treating adult castrated and 5α-dihydrotestosterone (DHT)-maintained male mice with different doses of oestrogens, as exposure of male mice to excessive amounts of oestrogens can cause bladder outlet obstruction (BOO); in addition, male mice lacking oestrogen receptor (ER)α (ERKO) or ERβ (BERKO) were studied to assess the importance of ER subtypes.


Castrated, DHT-maintained adult mice were treated with 17β-oestradiol (E2; 50 and 250 µg/kg) or oestrone (E1; 5, 50 and 500 µg/kg) daily for 10 days. Control mice were treated only with the vehicle. BERKO and ERKO mice, and their wild-type littermates used as their controls, remained untreated. Under anaesthesia, the bladder and distal urethra were exposed to record simultaneously the bladder pressure and urinary flow rate from the distal urethra.


E2-treated mice showed obstructive voiding, seen as increased bladder pressure, decreased average flow rate and prolonged micturition time. This was also evident when a high dose (500 µg/kg) of E1 was used. After treatment with a dose of 50 µg/kg, the urodynamic variables were similar to those in the control mice. Surprisingly, after treatment with a low dose (5 µg/kg) all urodynamic variables improved. There was a minor increase in the bladder pressure in BERKO mice; ERKO mice had a significantly lower urinary flow rate.


High doses of oestrogens caused BOO in castrated, DHT-maintained male mice. A small dose of E1 had a positive effect on voiding, suggesting that oestrogens are needed for normal male voiding. Reduced urinary flow rates in ERKO mice suggest that oestrogen effects on voiding are mediated at least partly via ERα.