Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue


George T. Kedia, Hannover Medical School, Division of Surgery, Department of Urology and Urological Oncology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. e-mail:


What's known on the subject? and What does the study add?

A previous study by Lexander et al. in 2005, using two-dimensional gel electrophoresis, demonstrated the expression of arginase type II in the different anatomical regions of the prostate; however, to date, no study has addressed, using an in vitro approach, the role of arginase isoenzymes in the human prostate.

The results of the present study demonstrate that: both arginase isoenzymes, Arg I and Arg II, are expressed in the transition zone of the human prostate; the inhibition of arginase antagonized, to a certain degree, the tension brought about by noradrenaline in isolated human prostate tissue; exposure of human prostate tissue to arginase inhibitors enhanced the local production of cyclic GMP; and inhibition of arginase enzymes in the human prostate may augment the activity of the nitric oxide/cyclicGMP pathway.


  • • To investigate the expression of arginase isoenzymes type I (Arg I) and type II (Arg II) in the transition zone of the human prostate and the functional significance of arginase enzymes in the control of prostate smooth muscle.


  • • Human prostate tissue was obtained from male patients who had undergone pelvic surgery.
  • • The expression of Arg I and Arg II was investigated using Western blot analysis.
  • • Using the organ bath technique, the effects of cumulative administration of difluoromethylornithine (DFMO), H-Orn-OH × HCl, H-Ile-OH and N-ω-hydroxy-nor-L-arginine (nor-NOHA; 1 nM–10 µM) on the tension induced by noradrenaline in isolated prostate tissue were assessed.
  • • Tissue strips were also exposed to arginase inhibitors and the production of cyclic GMP was determined.


  • • Western blot analysis showed the expression of Arg I and Arg II in the transition zone of the prostate.
  • • The tension induced by noradrenaline was antagonized by the drugs in the following rank order of efficacy: H-Orn-OH × HCl ≥ H-Ile-OH ≥ DFMO > nor-NOHA; however, the maximum reversion of tension recorded ranged from only −25 to −13%.
  • • The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors ranged from four- to 14-fold.


  • • Arg I and Arg II are expressed in the transition zone of the human prostate.
  • • Isometric tension studies and measurement of cyclic GMP showed that inhibition of arginase can reverse, to a certain degree, the tension of human prostate tissue induced by the activation of α-adrenoceptors and enhance the accumulation of cyclic GMP.
  • • Future studies should explore further the role of arginase enzymes in the relaxation mediated by nitric oxide in prostate smooth muscle.