Effect of letrozole on urinary bladder function in the female rabbit.
OBJECTIVE
To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry.


METHODS
Sixteen female New Zealand white rabbits were separated into four equal groups; groups 1-3 were given oral letrozole for 1, 2 and 3 weeks, and group 4 was given saline and served as the control group. At the end of the medication period each rabbit was anaesthetized and the bladder muscle strips were used for contractile, histological and biochemical studies.


RESULTS
The concentration of serum oestrogen was significantly lower and testosterone was significantly higher in letrozole-treated rabbits than in the control group. The rabbits treated for 1 week with letrozole showed significant decreases in the contractile responses to electrical field stimulation, ATP and carbachol, but not to KCl. Contractility returned to normal in the rabbits treated for 2 and 3 weeks. Letrozole resulted in an increased volume percentage of collagens and decreased bladder compliance. The volume percentage of the smooth muscle component also changed, with a significant decrease at 1 week and then a gradual increase at 2 and 3 weeks. Contractile dysfunction was absent at 2 and 3 weeks, which was consistent with no change in sarcoplasmic reticulum Ca(2+)-ATPase content or mitochondrial function.


CONCLUSIONS
The bladder contractility decline in the first week and was restored at 2 and 3 weeks. The present study unexpectedly showed the possibility that testosterone might be as important as oestrogen in the contractile function of the female bladder.
Lin
Wei-Yu
WY
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi, Taiwan, ROC, and Albany College of Pharmacy, Albany, NY, USA.
Rehfuss
Alexandra
A
Whitbeck
Catherine
C
Juan
Yung-Shun
YS
Chichester
Paul
P
Mannikarottu
Anita
A
Levin
Robert M
RM
D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood; D005260:Female; D000077289:Letrozole; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology*; D011817:Rabbits; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D013739:Testosterone; D000077289:Letrozole