Igdoura S A, Argraves W S, Morales C R
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
J Androl. 1997 Jul-Aug;18(4):400-10.
The low density lipoprotein receptor-related protein (LRP-1) is a multiligand receptor capable of mediating endocytosis of a wide array of ligands that relate to both lipoprotein metabolism and proteinase regulation. Many of its ligands are proteinases, proteinase-inhibitor complexes, and lipoproteins known to be contained within the luminal fluid of the seminiferous tubules or in the interstitial spaces of the testis. Immunocytochemical analysis was performed to characterize the pattern of expression of LRP-1 in cells of the rat testis. Immunoperoxidase staining localized LRP-1 to the cytoplasm of Sertoli cells. The distribution and intensity of the Sertoli cell staining was found to vary according to the stages of the cycle of the seminiferous epithelium. Staining was weak in the basal cytoplasm of Sertoli cells during stages II-VIII and strong and granular in the supranuclear cytoplasm during stages XII-XIV and stage I of the cycle. Immunogold labeling showed gold particles associated with the basal and adluminal plasma membranes, with endocytic vesicles, and with endosome membranes. Labeling was also observed on the plasma membrane and membranes of the endocytic apparatus in macrophages and Leydig cells in the interstitial space. Infusion of 125I-Labeled LRP-1 antibody into seminiferous tubules followed by radioautography showed silver grains overlaying the ad-luminal plasma membrane of Sertoli cells at time 0 and in endocytic vesicles and endosomes in the supranuclear region of Sertoli cells 10-minutes postinjection. When the 125I-Labeled LRP-1 antibody was injected into the interstitial space, silver grains overlayed the basal plasma membrane and coated endocytic pits of Sertoli cells at time 0 and, at 10 minutes, the grains labeled endosomes located in the basal pole of Sertoli cells. 125I-Labeled LRP-1 antibody also labeled the plasma membrane and the endocytic apparatus of macrophages and Leydig cells. The absence of immunogold labeling and radioautographic silver grains within lysosomes of Sertoli cells, Leydig cells, and macrophages suggests that internalized LRP-1 is recycled back to the cell surface. The presence of LRP-1 in the endocytic compartment of these cells is consistent with its functioning in the clearance of proteases involved in seminiferous tubule remodeling and/ or the uptake of cholesterol-bound lipoproteins necessary for the biosynthesis of testosterone. In conclusion, the results of these studies demonstrated for the first time the presence of LRP-1 receptor in the endocytic compartments of Sertoli cells and interstitial cells of the rat testis.
低密度脂蛋白受体相关蛋白（LRP-1）是一种多配体受体，能够介导多种与脂蛋白代谢和蛋白酶调节相关的配体的内吞作用。其许多配体都是蛋白酶、蛋白酶-抑制剂复合物以及已知存在于生精小管管腔液或睾丸间质空间中的脂蛋白。进行免疫细胞化学分析以表征LRP-1在大鼠睾丸细胞中的表达模式。免疫过氧化物酶染色将LRP-1定位到支持细胞的细胞质中。发现支持细胞染色的分布和强度根据生精上皮周期的阶段而变化。在周期的II-VIII阶段，支持细胞基底细胞质中的染色较弱，而在XII-XIV阶段和I阶段，核上细胞质中的染色较强且呈颗粒状。免疫金标记显示金颗粒与基底和近腔质膜、内吞小泡以及内体膜相关。在间质空间中的巨噬细胞和睾丸间质细胞的质膜和内吞装置膜上也观察到标记。将125I标记的LRP-1抗体注入生精小管，随后进行放射自显影，结果显示在注射后0分钟时，银粒覆盖在支持细胞的近腔质膜上，而在注射后10分钟时，银粒位于支持细胞核上区域的内吞小泡和内体中。当将125I标记的LRP-1抗体注入间质空间时，在注射后0分钟时，银粒覆盖在支持细胞的基底质膜和被包被的内吞小窝上，而在10分钟时，银粒标记位于支持细胞基底极的内体。125I标记的LRP-1抗体也标记了巨噬细胞和睾丸间质细胞的质膜和内吞装置。在支持细胞、睾丸间质细胞和巨噬细胞的溶酶体内未观察到免疫金标记和放射自显影银粒，这表明内化的LRP-1被循环回细胞表面。这些细胞内吞区室中存在LRP-1与其在清除参与生精小管重塑的蛋白酶和/或摄取睾酮生物合成所需的胆固醇结合脂蛋白方面的功能一致。总之，这些研究结果首次证明了LRP-1受体在大鼠睾丸支持细胞和间质细胞的内吞区室中的存在。
