Infravesical Obstruction in Aromatase Over Expressing Transgenic Male Mice With Increased Ratio of Serum Estrogen-To-Androgen Concentration

Abstract

The potential role of estrogen in the development of infravesical obstruction is still unresolved. Aromatase over expressing transgenic mice provide a novel instrument for investigating the consequences of prolonged systemic or local increases in endogenous estrogen concentrations. Two aromatase over expressing transgenic mouse strains with different prostatic phenotypes (reduced and normal size, respectively) were compared in urodynamic studies with each other and with the wild-type strain. The bladder and urethra were exposed in adult male wild-type or transgenic mice. High frequency oscillations of intraluminal bladder pressure and flow rate from the distal urethra were simultaneously recorded with the mice under anesthesia. No changes were observed in voiding in MMTV-arom+ mice. These mice are known to have only slightly elevated estradiol concentrations in serum, suggesting a localized increase in estrogen production. In AROM+ mice the aromatase gene was detected in several organs, including the testis and bladder. These mice are known to have markedly increased estrogen and decreased serum androgen concentrations, and reduced prostate size. Compared with wild-type mice AROM+ mice showed higher mean maximal bladder pressure plus or minus standard deviation (33.1 +/- 6.4 versus 25.6 +/- 4.8 mm. Hg, p = 0.046) and decreased mean maximal flow rate (3.1 +/- 1.6 versus 17.7 +/- 5.4 ml. per minute, p <0.0001), consistent with the presence of the infravesical obstruction. Morphologically the proximal rhabdosphincter in AROM+ mice showed atrophy (relative mean thickness 0.005 +/- 0.015 versus 0.013 +/- 0.002 mm., p <0.0001). Activation of the aromatase gene during an earlier developmental stage under the ubiquitin C promoter and highly elevated serum estrogen concentrations may explain the differences in voiding and prostate size in the AROM+ mouse strain.