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Keywords:

  • Kininases;
  • kinins;
  • tissue kallikrein;
  • bradykinin receptor;
  • infertility

Summary. All four components of the kallikrein-kinin system—kininogens, tissue kallikreins, kinins, and kininases—have been found in human male genital secretions. Kinins are continuously released from seminal plasma kininogens through limited proteolysis by kininogenases like tissue kallikrein from prostate and sperm acrosin. Kinins are the terminal effectors of the kallikrein-kinin system and increase sperm motility and sperm metabolism at nanomolar concentrations. Recent investigations indicate that these effects are possibly mediated by a specific sperm membrane integrated bradykinin receptor, subtype B2. The two major kininases that are present in seminal plasma are kininase II and neutral metallo-endopeptidase. Kininase II, which is identical with angiotensin-converting enzyme, is also involved in the renin-angiotensin system as it converts angiotensin I into angiotensin II and thus is the connecting enzyme of both systems. Apart from the observed effects of kinins on sperm motility, the kallikrein-kinin system is thought to be involved in the regulation of spermatogenic functions of the testis: in the rat, kallikrein activates Sertoli cell function, increases the relative number of spermatocytes and the [3H] thymidine incorporation of testicular tissue, enhances glucose-intake, and increases testicular blood flow. Clinical trials showed that systemic administration of kallikrein may be particularly useful for treatment of infertile men suffering from asthenozoospermia and/or oligozoospermia. During kallikrein therapy, the number of spermatozoa and both quantitative and qualitative sperm motility increased, and a significant improvement of the conception rate was achieved. An increased sperm number was also observed after application of the specific kininase II inhibitor captopril. Recent investigations proved intestinal absorption of porcine pancreatic kallikrein in men, supporting the clinical effectiveness of oral kallikrein therapy. Furthermore, the results indicate that absorbed kallikrein may be enzymatically active for hours in serum. Thus, according to the various in vitro experiments, animal studies, and clinical trials, there is increasing evidence that the kallikrein-kinin system is involved in male reproductive functions.