Effect of Testosterone on Epithelial Cell Proliferation in the Regressed Rat Epididymis

It is well established that testosterone plays a crucial role in maintaining the integrity of epididymal structure and function. However, the role of testosterone in restoring the cellular architecture of the regressed epididymis is not well known. The present study was undertaken to test the hypothesis that testosterone triggers the regressed epididymis by re-expanding existing cells and inducing cell proliferation. Testosterone-dependent epididymal morphology was evaluated in orchidectomized, regressed rats after initiation of treatment with testosterone. Besides that, the proliferative activity of epithelial cells in all regions of the epididymis of the orchidectomized, regressed rats was assessed at 1, 3, 7, and 28 days after testosterone replacement. Epithelial cell proliferation decreased after testosterone withdrawal and increased following testosterone administration. We found that bromodeoxyuridine incorporation and proliferating nuclear antigen expression increased significantly 3 days after testosterone replacement in all regions of the regressed epididymis except in the initial segment. The highest mitotic activity was seen in the corpus epididymidis at 3 days postimplantation. Using specific markers for each cell type, we found no significant changes in the proportion of each cell type compared with the control. We observed labeled nuclei in all epithelial cell types in the control; however, principal cells were the major cell types that responded to testosterone after regression. These observations demonstrate that the mammalian epididymis is not a static tissue without any significant cell renewal, either under control conditions or when androgen exposure is altered, thus providing new insight in the role of androgen in restoration and maintenance of the architecture of the epididymis.