Effect of letrozole on urinary bladder function in the female rabbit

Abstract

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. MATERIALS AND 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 Ca2+‐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.

Aromatase expression is linked to estrogenic sensitivity of periurethral muscles in female rabbits

“…On the contrary, the Bsm seems to be less estrogen‐dependent and, possibly, more dependent of endocrine or local actions of androgens . Considering the role of the Pcm and Bsm during micturition in rabbits, it could be proposed that the impairment in estrogen signalling, including aromatase expression, affects more the storage than the voiding phase of micturition . Given that the lack of the peak serum estradiol at late pregnancy is not present in multiparous rabbits, we propose that the local steroidogenesis could supply estrogens and even androgens participating in processes required to sustain the function of the Pcm and Bsm .…”

“…42,43 Considering the role of the Pcm and Bsm during micturition in rabbits, it could be proposed that the impairment in estrogen signalling, including aromatase expression, affects more the storage than the voiding phase of micturition. 17,44 Given that the lack of the peak serum estradiol at late pregnancy is not present in multiparous rabbits, we propose that the local steroidogenesis could supply estrogens and even androgens participating in processes required to sustain the function of the Pcm and Bsm. 18,19 Moreover, present findings may help to elucidate the impact of menopause in pelvic floor dysfunctions and to attain a more precise description of estrogen actions relevant for designing adequate estrogen-based treatments.…”

Exogenous Testosterone and Estrogen Affect Bladder Tissue Contractility and Histomorphology Differently in Rat Ovariectomy Model

“…Only five studies in previously published literature investigated the possible role of testosterone on female bladder tissue (Table 1) [4–8]. Unfortunately two of these studies which were conducted by Lin et al.…”

“…Unfortunately two of these studies which were conducted by Lin et al. [4] and Cayan et al. [6], concentrated only on both smooth muscle physiology and histology; the rest were limited to histomorphological assessment.…”

“…In contrast to these two facts, most of experimental models ignore the existence of testosterone in the female body and suggest that ovariectomy should mimic menopause in an experimental animal model. Thus, all changes associated with menopause, in the bladder, are attributed to estrogen deficiency in animal ovariectomy models; only a few animal experiments studied the effect of testosterone withdrawal with supraphysiological testosterone levels (Table 1) [4–7].…”