INVESTIGATIVE UROLOGY

A dose-dependent dual effect of oestrogen on voiding in the male mouse?
Streng TK, Talo A, Andersson KE, Santti R
Department of Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
BJU Int. 2005; 96: 1126-30

• Objectives: To explore the effect of different degrees of oestrogenization on male voiding, by treating adult castrated and 5alpha-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)alpha (ERKO) or ERbeta (BERKO) were studied to assess the importance of ER subtypes.
• Materials and Methods: Castrated, DHT-maintained adult mice were treated with 17beta-oestradiol (E(2); 50 and 250 microg/kg) or oestrone (E(1); 5, 50 and 500 microg/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.
• Results: E(2)-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 microg/kg) of E(1) was used. After treatment with a dose of 50 microg/kg, the urodynamic variables were similar to those in the control mice. Surprisingly, after treatment with a low dose (5 microg/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.
• Conclusions: High doses of oestrogens caused BOO in castrated, DHT-maintained male mice. A small dose of E(1) 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 ERalpha.
  
  
• Editorial Comment
  Previous investigation using neonatal DES treatment demonstrated that vesical smooth muscle contractility was not significantly affected (1). However, our results (2) showed that neonatal DES led to a significant vesical extracellular matrix remodeling, which is in line with reports using infravesical surgical obstruction (3,4). Thus, neonatal DES may be an adequate vesical obstruction model, at least with regard to extracellular matrix changes.
  The results of the present well done investigation suggest that the effects of estrogens may be dual and dose-dependent. The authors confirmed the obstructive effect of high doses of E2 in adult castrated male mice maintained with DHT. On the other hand, when the mice were treated with the low dose of E1 the variables measured showed no sign of obstructive voiding. The ERKO mice had lower urinary flow rates and the BERKO mice had a higher mean bladder pressure than their wild-type littermates used as controls. As conclusion, the authors proposed that apart of high doses of estrogens determine obstruction; estrogens may be also needed for normal voiding of the male mouse.

References
1. Longhurst PA: In vitro rat bladder function after neonatal estrogenization. J Urol. 2002; 168: 2695-9.
2. Cabral C, Silva E, Sampaio FJ, Cardoso L: Compositional changes in vesical extracellular matrix in male rats after neonatal estrogenization with diethylstilbestrol. Eur Urol. 2004; Suppl 3, No. 2: Abst #298, pp. 77.
3. Uvelius B, Mattiasson A: Collagen content in the rat urinary bladder subjected to infravesical outflow obstruction. J Urol. 1984; 132: 587-90.
4. Kim JC, Yoon JY, Seo SI, Hwang TK, Park YH: Effects of partial bladder outlet obstruction and its relief on types I and III collagen and detrusor contractility in the rat. Neurourol Urodyn. 2000; 19: 29-42.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil