Hormone-induced activation of target-specific lysosomes: acute translocation to the nucleus after administration of gonadal hormones in vivo.

Abstract

SUMMARY Recent evidence from these laboratories has implicated the primary lysosomal population of specific target cells in the selective reception of steroid hormones at the cell periphery. This phenomenon was shown to be associated with covert labilization of the lysosomal bounding membrane. It has now been demonstrated that this interaction with trophic hormones results in rapid migration of lysosomes to a perinuclear position. Suspensions of nuclei were isolated from preputial glands of ovariectomized rats within short intervals after administration of gonadal hormone in vivo. Identification of cellular organelles by ultraviolet fluorescence microscopy was carried out on preparations subjected to intravital staining in vitro with acridine orange. Lysosomes were present in high concentrations in nuclear fractions of preputial glands from animals pretreated with oestradiol-17β, diethylstilboestrol, or testosterone, and essentially absent in preparations obtained from animals injected with oestradiol-17α or control solution. The response could be detected within 1 min of hormone administration, was obtained with as little as 0·1 μg hormone/100 g body wt, and was not observed in preparations from lung tissue. In the early stages of hormonal activation, lysosomes in preputial gland preparations formed adherent perinuclear clusters and appeared relatively intact. However, lysosome fragmentation and dissolution rapidly ensued and was accompanied by the appearance of polynuclear—multilysosomal aggregates. Concomitantly, isolated lysosome preparations subjected to enzymatic analyses revealed increased release from the particle-bound form of hydrolytic enzymes characteristic of these organelles. Progressive nuclear metachromasy was also observed after administration of the active hormones, suggesting the breakdown of macromolecules which yield products with enhanced capacity for binding acridine orange. These results suggested that modification of the nuclear surface and of intranuclear constituents, leading to altered adhesiveness and dye binding, respectively, may reflect the activity of structurally latent hydrolases released in situ from lysosomal membranes labilized by exposure to hormone. The present results support the concept that lysosomal function may be involved in the coupling of initial steroid—receptor interaction at the cell membrane with hormone-dependent events in specific target cells.