Barrier function of microvessels and roles of glial cell line-derived neurotrophic factor in the rat testis

Abstract.

 The expression and localization of glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 in the testis were examined, because the blood-testis barrier is a well-known tissue barrier and we previously reported that GDNF reduced the endothelial permeability of the blood–brain barrier (BBB). Five minutes after intravenous injection of Evans blue (molecular weight, 960.6) or fluorescent dextran (molecular weight 10 000 and 70 000), Evans blue was observed outside microvessels of the testis, whereas the fluorescent dextran was not. Immunohistochemically, GDNF was detected in alpha-smooth muscle actin-positive cells around the seminiferous tubules and in microvessels. On the other hand, GFRα1 was detected in endothelial cells in the interstitial space, as well as in spermatocytes. Although occludin was positive in Sertoli cells and endothelium, claudin-5 was localized only in the endothelium of the microvessels. Thus, it became very clear that the microvessels in the testis possessed relatively impermeable tight junctions, and that the alpha-smooth muscle actin-positive cells secreted GDNF, which receptor was expressed in endothelial cells. Because this relation between GDNF and GFRα1 is similar to that observed in the BBB, we hypothesize that GDNF is a general regulator of tight junctions of the endothelium forming a blood–tissue barrier in a paracrine fashion.