A pharmacological manipulation of testicular function for rational therapeutic approach to male infertility: Experimental and clinical data.

Abstract

A pharmacological manipulation of testicular function in rats was attempted to increase our understanding on pathogenesis of male infertility, thereby establishing a rationale in management of male infertility. The testicular functions in rats were evaluated after the treatment with kallikrein (KAL) or other agents in the light of testicular blood flow (TBF) by hydrogen gas clearance method, responsiveness of Leydig cells upon gonadotropin stimulation and androgenbinding protein (ABP) by steady state polyacrylamide gel electrophoresis.<br>TBF in rats was significantly increased either by the treatment with KAL (29.2±1.7) or hydralazine (HLZ)(27.2±1.7) as compared with the control (17.5±1.5ml/min/100g tissue)(p<0.01). Neither basal testosterone level nor responsiveness of Leydig cells on gonadotropin stimulation was affected by KAL.<br>Significantly higher binding capacity of ABP in the testicular cytosole of rats (0.26±0.01) was noted with the KAL treatment as compared with either the control (0.21±0.01) or the HLZ treatment (0.22±0.02pmol/mg protein)(p<0.01). These results indicated that KAL activated the Sertoli cell function independent of TBF.<br>Based on the results of experimental studies, the kallikrein treatment for oligospermic patients without varicocele and for those with varicocele who failed to improve the semen quality after varicocelectomy was attempted.<br>Thirty-nine per cent of oligospermic patients without varicocele showed two-fold increase in sperm density after the KAL treatment. Two-fold increase in sperm density was also noted in 45% of patients treated by varicocelectomy only, and in 55% by the treatment with KAL in patients who failed to be improved by varicocelectomy.<br>Conclusion: Kallikrein activates the Sertoli cell function. Because the Sertoli cell dysfunction shares to some extent the basic pathogenesis of male infertility, a pharmacological manipulation of Sertoli cells (i.e. KAL treatment) can be attempted as a treatment for male infertility with varicocele.

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