LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN-1 EXPRESSION IN THE TESTIS - REGULATED EXPRESSION IN SERTOLI CELLS

The low density lipoprotein receptor-related protein (LRP-1) is a mult iligand receptor capable of mediating endocytosis of a wide array of l igands that relate to both lipoprotein metabolism and proteinase regul ation. Many of its ligands are proteinases, proteinase-inhibitor compl exes, and lipoproteins known to be contained within the luminal fluid of the seminiferous tubules or in the interstitial spaces of the testi s. Immunocytochemical analysis was performed to characterize the patte rn of expression of LRP-1 in cells of the rat testis. Immunoperoxidase staining localized LRP-1 to the cytoplasm of Sertoli cells. The distr ibution and intensity of the Sertoli cell staining was found to vary a ccording to the stages of the cycle of the seminiferous epithelium. St aining was weak in the basal cytoplasm of Sertoli cells during stages Il-VIII and strong and granular in the supranuclear cytoplasm during s tages XII-XIV and stage I of the cycle. Immunogold labeling showed gol d particles associated with the basal and adluminal plasma membranes, with endocytic vesicles, and with endosome membranes. Labeling was als o observed on the plasma membrane and membranes of the endocytic appar atus in macrophages and Leydig cells in the interstitial space. Infusi on of I-125-Labeled LRP-1 antibody into seminiferous tubules followed by radioautography showed silver grains overlaying the adluminal plasm a membrane of Sertoli cells at time 0 and in endocytic vesicles and en dosomes in the supranuclear region of Sertoli cells 10-minutes postinj ection. When the I-125-Labeled LRP-1 antibody was injected into the in terstitial space, silver grains overlayed the basal plasma membrane an d coated endocytic pits of Sertoli cells at time 0 and, at 10 minutes, the grains labeled endosomes located in the basal pole of Sertoli cel ls. I-125-Labeled LRP-1 antibody also labeled the plasma membrane and the endocytic apparatus of macrophages and Leydig cells. The absence o f immunogold labeling and radioautographic silver grains within lysoso mes of Sertoli cells, Leydig cells, and macrophages suggests that inte rnalized LRP-1 is recycled back to the cell surface. The presence of L RP-1 in the endocytic compartment of these cells is consistent with it s functioning in the clearance of proteases involved in seminiferous t ubule remodeling and/or the uptake of cholesterol-bound lipoproteins n ecessary for the biosynthesis of testosterone. In conclusion, the resu lts of these studies demonstrated for the first time the presence of L RP-1 receptor in the endocytic compartments of Sertoli cells and inter stitial cells of the rat testis.