Source, catabolism and role of the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro within the testis

The tetrapeptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) is a natura l regulator of hematopoietic stem cell proliferation, The present study was aimed at investigating the presence and the role of AcSDKP in rat testis, Specific immunoreactivity was always observed in the interstitial tissue at all stages of testicular development and in elongated spermatids at 45 day s of age and in adults. In accordance with the interstitial labeling, high AcSDKP levels were detected in Leydig cell and testicular macrophage cultur e media and cell extracts, as well as in the testicular interstitial fluid (TIF), Much lower concentrations were found in peritubular cells and Sertol i cells cultures, whereas very low concentrations were present in cultured spermatocytes and spermatids. In contrast to the slight degradation rate of AcSDKP observed in the spermatocyte and spermatid culture media, no catabo lism of the peptide was seen in testicular somatic cell culture medium. Fur thermore, the degradation rate of AcSDKP was much lower in TIF than in peri pheral blood plasma. Despite the very strong evidence indicating that Leydi g cells and testicular macrophages produce AcSDKP, the selective destructio n of these cells did not result in any change in AcSDKP levels in TIF or in plasma. This suggests a compensatory mechanism ensuring constant levels of the peptide in TIF when interstitial cells are absent. Finally, in vitro, in the presence of AcSDKP, significantly more [H-3]thymidine incorporation was found in A spermatogonia, In conclusion, this study establishes the pre sence of very high concentrations of AcSDKP in rat testis and demonstrates its Leydig cell and testicular macrophage origin. The presence of AcSDKP in the TIF and its stimulatory effect on thymidine incorporation in spermatog onia very strongly suggest its implication in the paracrine control of sper matogenesis.