Glutathione-Related Enzymes in Cell Cultures From Different Regions of Human Epididymis

Abstract

Protection of maturing sperm from potential endogenous or exogenous harmful substances during their transit throughout the epididymis is a critical event. The authors studied the activity of gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST), and glutathione (GSH) levels in epithelial cell cultures from human caput, corpus, and cauda epididymides. Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Enzymatic activity was measured in conditioned media and cellular fractions. Androgen influence was also evaluated. Both enzymatic activities were found in cellular homogenates and conditioned media from cultures of all epididymal regions. GGT activity was highest in cultures from cauda epididymis, both in conditioned media and cell fractions, while GST activity did not show regional differences in conditioned media, but exhibited higher activity in cell homogenates from cauda cultures than those obtained from corpus and caput epididymis. GSH level showed no regional difference in cell homogenates and it could not be detected in conditioned media by the method used. Presence of different concentrations of dihydrotestosterone (DHT) had no influence neither on the enzymatic activities nor GSH concentration. The results indicate that GGT and GST are present along the human epididymis and a fraction or isoform of these enzymes might be secreted to the luminal fluid to play a detoxificative role in sperm maturation.

Epididymis Response Partly Compensates for Spermatozoa Oxidative Defects in snGPx4 and GPx5 Double Mutant Mice

“…Finally, together with thioredoxins and peroxiredoxin 3, we have found that glutathione-S-transferases (GSTπ and GSTµ) are also significantly up-regulated both in the caput and cauda epididymidis compartments of the double mutant animals. This agrees with previous reports showing that GSTs are expressed at significant levels in mammalian epididymis [31], [42]. Induced expression of multiple forms of GST appears to be an evolutionary response of cells to protect against chemical toxicity and oxidative stress.…”

Glutathione peroxidase activity in cell cultures from different regions of human epididymis

“…The opposite has been reported for the GPx5 in the rat and mouse, in which the gene is expressed mainly in the initial segment and caput epididymis [6,8]. We have found the same difference between rats and men in other GSH related enzymes [20], suggesting that the genetic regulatory mechanism, an influence of testicular factors (which are not present in cultured cells), may be different in both species. However, androgen control of human epididymal GPx activity seems to be similar to other species studied [7].…”

Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

“…Epididymis plays important roles in sperm maturation, motility, and storage (21). The activity of some detoxifying enzymes such as gamma-glutamyltranspeptidase (GGT) and glutathione S-transferase (GST) was detected in epithelial cell culture of human epididymis (22). In epididymis of male Nrf2-knockout mice, lipid peroxidation increased, and expression of GST, sod2, and enzymatic activities of glutathione reductase and glutathione peroxidase decreased (9).…”