The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice

Abstract

This investigation aimed to see whether a change in the oestrogen to androgen ratio alters prostate contractility. Isolated organ bath studies using prostates from aromatase knockout (ArKO) mice which were homozygous (ArKO-/-) and heterozygous (ArKO+/-) for the disrupted aromatase cyp19 gene and wild-type littermates (ArKO+/+) were conducted. The distribution of noradrenergic nerves was visualized using the sucrose-potassium phosphate-glyoxylic acid method. ArKO-/- mice had increased prostate weights compared with ArKO+/+ mice. Frequency-response curves to electrical field stimulation (EFS; 0.5 ms pulse duration, 60 V, 0.1-20 Hz) yielded frequency-dependent contractions, while noradrenaline (10 nM-1 mM) and tyramine (1 muM-1 mM) produced concentration-dependent contractions. Prazosin (0.3 muM) attenuated the responses induced by noradrenaline and EFS in all mice (P</=0.019, n=5-7), while cocaine (10 muM) attenuated the responses evoked by tyramine (P<0.001, n=6). There were no genotype differences in EFS- and noradrenaline-induced responses (P>/=0.506, n=10-13). Prostates from ArKO-/- and ArKO+/- mice were more sensitive to tyramine than prostates from ArKO+/+ mice (P<0.001, n=11-13). Dense adrenergic innervation of the prostate was similar in all mice. These results suggest that although the absence of aromatase increases prostatic growth, this translates only to a subtle and selective increase in contractility in mature mice.