Steroid Hormones as Transporters to Carry Exogenous Macromolecules into the Target Cell Nuclei in Vivo

Abstract

Abstract:Upon injection into the vascular system of rats, testosterone-bovine serum albumin conjugate (testosterone-BSA) is taken up by cells via the process of endocytosis. When it is taken up by the target cells of testosterone such as spermatogenic cells, it enters the nuclei of the cells. However, testosterone-BSA does not enter the nuclei of the non-target cells such as hepatocytes and thymocytes. Similarly, hydrocortisone-BSA conjugate enters the nuclei of its target cells such as hepatocytes and thymocytes. In the vesicular trafficking of testosterone-BSAs into the nucleoplasm, the vesicle membrane is likely to fuse with a nuclear hemifusion diaphragm. IgG coupled with hydrocortisone also enters the hormone-target cell nuclei, with its antigenicity kept intact. These results suggest that steroid hormones could act as transporters for conveying exogenous macromolecules into the target cell nuclei in vivo. Our studies provide a novel insight to the functions of steroid hormones.

Transportation Course of Macromolecules to the Nucleus from the Extracellular Environment: Steroid Hormones’ Cellular Entry Mode Revisited

“…In contrast, SV40-containing vesicles with ferritin particles were observed close to a single-bilayer nuclear membrane or a diaphragm (Figure 1b, c) [9,10]. The nucleoplasmic side of the diaphragm was covered with electron-dense materials, and cell membrane markers were localized along the Environment: Steroid Hormones' Cellular Entry Mode Revisited nucleoplasmic side of the inner nuclear membrane [9,10]. These results suggest that SV40-containing vesicle membrane fuses to a single-bilayer diaphragm in the nuclear envelope in order to transport virus particles into the nucleoplasm, and that the exogenous macromolecules used here as cell membrane markers were transported into the nucleus in this manner ( Figure 1b) [9].…”

“…In observations without silver enhancement, a single-bilayer nuclear membrane or a diaphragm was visible in the SNE [10,13]. In post-acrosomal nuclear envelope, the outer nuclear membrane was invaginated toward the inner nuclear membrane, and was likely to interact with the latter (Figure 1e) [10,21]. Furthermore, a double-membrane-like vesicle containing gold particles was observed in the pit formed by the invagination of the outer nuclear membrane (Figure 1e) [10,21].…”

“…Ferritin particles introduced into the cytoplasm did not enter the nucleus by themselves. In contrast, SV40-containing vesicles with ferritin particles were observed close to a single-bilayer nuclear membrane or a diaphragm (Figure 1b, c) [9,10]. The nucleoplasmic side of the diaphragm was covered with electron-dense materials, and cell membrane markers were localized along the Environment: Steroid Hormones' Cellular Entry Mode Revisited nucleoplasmic side of the inner nuclear membrane [9,10].…”

“…In the spermatogenic cells of rat injected with testosterone-BSA-gold, the silver deposits were present on the cell membrane, vesicles, Golgi region, acrosome, subacrosomal space, both the post-acrosomal and the subacrosomal nuclear envelope, and the nucleoplasm [10,21]. In observations without silver enhancement, a single-bilayer nuclear membrane or a diaphragm was visible in the SNE [10,13]. In post-acrosomal nuclear envelope, the outer nuclear membrane was invaginated toward the inner nuclear membrane, and was likely to interact with the latter (Figure 1e) [10,21].…”

“…Colloidal gold embedded in epoxy resin becomes visible as silver deposits on the sections after silver enhancement [20]. Upon injection into the vascular system of rats, testosterone-bovine serum albumin conjugate labeled with 2 nm colloidal gold (testosterone-BSA-gold) is taken up by endocytosis into the target cells of testosterones such as round spermatids, and then enters the nucleoplasm [10,20,21]. In contrast, the nuclei of cells that are not targeted by testosterone such as thymocytes and hepatocytes showed very few silver deposits implying the presence of testosterone-BSA-gold [20].…”