Abstract
Glial tumor cells are known to be sensitive to glucocorticoids (GC) in vivo and in vitro. Here we studied the expression of corticosteroid-binding globulin (CBG) in the low-grade malignant human astrocytoma cell line 1321N1. CBG was observed in cytoplasm of most of these cells with immunocytochemistry. RT-PCR revealed the presence of the respective mRNA. Only scattered cells contained nuclear immunoreactivity for glucocorticoid receptor as visualized by double immunostaining. Immunoreactive CBG could be recovered from the supernatant of cultures that had been exposed to 10−5 M cortisol. Our observations indicate the endogenous expression of CBG in 1321N1 cells which may occur independently from classical glucocorticoid receptor pathways. Cortisol seems to facilitate liberation of CBG in a paracrine manner, perhaps through membrane action of the steroid. Effects of adrenal steroids on proliferation and apoptosis of certain glial tumors may in part depend on these mechanisms.
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References
Allera A, Wildt L (1992) Glucocorticoid-recognizing and -effector sites in rat liver plasma membrane. Kinetics of corticosterone uptake by isolated membrane vesicles-II. Comparative influx and efflux. J Steroid Biochem Mol Biol 42:757–771. doi:10.1016/0960-0760(92)90116-Z
Beato M, Herrlich P, Schutz G (1995) Steroid hormone receptors: many actors in search of a plot. Cell 83:851–857. doi:10.1016/0092-8674(95)90201-5
Bob P, Fedor-Freybergh P, Jasova D, Bizik G, Susta M, Pavlat J, Zima T, Benakova H, Raboch J (2008) Dissociative symptoms and neuroendocrine dysregulation in depression. Med Sci Monit 14:499–504
Bourke E, Moynagh PN (1999) Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B. J Immunol 163:2113–2119
Caldwell JD, Shapiro RA, Jirikowski GF, Suleman F (2007) Internalization of sex hormone-binding globulin into neurons and brain cells in vitro and in vivo. Neuroendocrinology 86:84–93. doi:10.1159/000107072
Carroll RS, Zhang J, Dashner K, Sar M, Black PM (1995) Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:496–503
Crossin KL, Tai MH, Krushel LA, Mauro VP, Edelman GM (1997) Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation. Proc Natl Acad Sci USA 94:2687–2692. doi:10.1073/pnas.94.6.2687
De Kloet ER, McEwen BS (1976) A putative glucocorticoid receptor and a transcortin-like macromolecule in pituitary cytosol. Biochim Biophys Acta 421:115–123
Demey-Ponsart E, Foidart JM, Sulon J, Sodoyez JC (1982) Serum CBG, free and total cortisol and circadian patterns of adrenal function in normal pregnancy. J Steroid Biochem 16:165–169. doi:10.1016/0022-4731(82)90163-7
Dey R, Roychowdhury P (2003) Homology model of human corticosteroid binding globulin: a study of its steroid binding ability and a plausible mechanism of steroid hormone release at the site of inflammation. J Mol Model 9:183–189. doi:10.1007/s00894-003-0130-4
Emptoz-Bonneton A, Crave JC, LeJeune H, Brébant C, Pugeat M (1997) Corticosteroid-binding globulin synthesis regulation by cytokines and glucocorticoids in human hepatoblastoma-derived (HepGs) cells. J Clin Endocrinol Metab 82:3758–3762
Foster SJ, Perkins JP (1977) Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E1. Proc Natl Acad Sci USA 74:4816–4820
Gao G, Herbert Z, Kong J, Gabrielson N, Mautz A, Wu D, Gustav F, Jirikowski GF, Caldwell JD (2003) Estradiol control of expression and levels of estradiol binding proteins in the medial preoptic area, medial hypothalamus and pituitary. Neuroendocrinology 78:61–71
Hammond GL, Smith CL, Underhill DA (1991) Molecular studies of corticosteroid binding globulin structure, biosynthesis and function. J Steroid Biochem Mol Biol 40:755–762
Herbert Z, Pollak E, Molnar L, Caldwell JD, Jirikowski GF (2006) Co-transport of sex hormone-binding globulin SHBG with oxytocin in transport vesicles of the hypothalamo-hypophysial system. Horm Metab Res 38:291–293
Inoue T, Akahira J, Suzuki T, Darnel AD, Kaneko C, Takahashi K, Hatori M, Shirane R, Kumabe T, Kurokawa Y, Satomi S, Sasano H (2002) Progesterone production and actions in the human central nervous system and neurogenic tumors. J Clin Endocrinol Metab 87:5325–5331
Jirikowski GF, Pusch L, Mopert B, Herbert Z, Caldwell JD (2007) Expression of corticosteroid binding globulin in the rat central nervous system. J Chem Neuroanat 34:22–28
Lewis JG, Lewis MG, Elder PA (2003) An enzyme-linked immunosorbent assay for corticosteroid-binding globulin using monoclonal and polyclonal antibodies: decline in CBG following synthetic ACTH. Clin Chim Acta 328:121–128
Lindenbaum M, Chatterton RT Jr (1981) Interaction of steroids with dexamethasone-binding receptor and corticosteroid-binding globulin in the mammary gland of the mouse in relation to lactation. Endocrinology 109:363–375
Maitra US, Khan MS, Rosner W (1993) Corticosteroid-binding globulin receptor of the rat hepatic membrane: solubilization, partial characterization, and the effect of steroids on binding. Endocrinology 133:1817–1822
Malaplate-Armand C, Ferrari L, Masson C, Visvikis-Siest S, Lambert H, Batt AM (2005) Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells. Toxicol Lett 159:203–211
Mead C, Pentreath VW (1998) Evaluation of toxicity indicators in rat primary astrocytes, C6 glioma and human 1321N1 astrocytoma cells: can gliotoxicity be distinguished from cytotoxicity? Arch Toxicol 72:372–380
Misao R, Nakanishi Y, Fujimoto J, Tamaya T (1998) Effects of sex steroid hormones on corticosteroid-binding globulin gene expression in human endometrial cancer cell line Ishikawa. Ann Clin Biochem 35:637–642
Möpert B, Herbert Z, Caldwell JD, Jirikowski GF (2006) Expression of corticosterone-binding globulin in the rat hypothalamus. Horm Metab Res 38:246–252
Paoletti P, Butti G, Zibera C, Scerrati M, Gibelli N, Roselli R, Magrassi L, Sica G, Rossi G, Robustelli della Cuna G (1990) Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors. J Neurosurg 73:736–742
Predine J, Brailly S, Delaporte P, Milgrom E (1984) Protein binding of cortisol in human cerebrospinal fluid. J Clin Endocrinol Metab 58:6–11
Sivukhina EV, Jirikowski GF, Bernstein HG, Lewis JG, Herbert Z (2006) Expression of corticosteroid-binding protein in the human hypothalamus, co-localization with oxytocin and vasopressin. Horm Metab Res 38:253–259
Webster JC, Huber RM, Hanson RL, Collier PM, Haws TF, Mills JK, Burn TC, Allegretto EA (2002) Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types. Endocrinology 143:3866–3874
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Pusch, L., Wegmann, S., Caldwell, J.D. et al. Expression of Corticosteroid-Binding Globulin in Human Astrocytoma Cell Line. Cell Mol Neurobiol 29, 583–588 (2009). https://doi.org/10.1007/s10571-009-9350-1
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DOI: https://doi.org/10.1007/s10571-009-9350-1