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

J Endocrinol. 2007 Dec;195(3):495-502. doi: 10.1677/JOE-07-0411.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Fibers / metabolism
  • Animals
  • Aromatase / deficiency*
  • Aromatase / genetics
  • Catecholamines / metabolism
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Heterozygote
  • Homozygote
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Knockout / genetics
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Norepinephrine / administration & dosage
  • Norepinephrine / pharmacology*
  • Organ Size
  • Osmolar Concentration
  • Prostate / anatomy & histology
  • Prostate / drug effects*
  • Prostate / innervation
  • Prostate / physiology*
  • Staining and Labeling
  • Tyramine / administration & dosage
  • Tyramine / pharmacology

Substances

  • Catecholamines
  • Aromatase
  • Norepinephrine
  • Tyramine