Glucocorticoids modulate renal glucocorticoid receptors and Na
Asics outlet asics store online k ATPase activity
Demetrius Ellis1, Tran Dang Sothi1 and Ellis D Avner1
1Nephrology Laboratory, Children’s Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Correspondence: Demetrius Ellis MD, Director of Nephrology, Children’s Hospital of Pittsburgh, One Children’s Place, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, Pennsylvania 152133417, USA.
Received 16 October 1986; Revised 12 March 1987.
Top of pageAbstractK ATPase activity. Primary cultures of mouse renal tubular epithelial cells were used to study the effect of hydrocortisone on the regulation of glucocorticoid receptors (GR) and on sodium adenosine triphosphatase (NaK ATPase) activity. A GR assay was developed and performed directly on cell monolayers maintained in serum medium to which hydrocortisone at 5 nM, 50 nM, and 5 104 M was added. Compared with control cells grown in medium without hydrocortisone, GR levels per cell decreased by 50% after 48 hours of growth in medium containing 5 nM hydrocortisone. After 96 hours of cell treatment with supraphysiologic hydrocortisone concentrations (50 nM or 5 104 M), GR levels decreased to 28% of control values. In all hydrocortisone treatment groups there was an inverse relation between GR concentrations and NaK ATPase activity. Binding of cell GR by the addition of the antiglucocorticoid RU 38486 in hydrocortisone medium eliminated the glucocorticoid stimulation of NaK ATPase activity. These results demonstrate a time and dose effect of glucocorticoids on GR binding activity and a direct relation between this receptor interaction and NaK ATPase activity in intact renal tubular epithelial cells.
Top of pageReferences
Liggins GC: Premature delivery of asics store online foetal lamb infused with glucocorticoids. J Endocrinol 45:515 1969 PubMed ISI ChemPort Liggins GC: Adrenocortical related maturational events in the fetus. Am J Obstet Gynecol 126:932 1976Cheek DB, Graystone JE, Niall M: Factors controlling fetal growth. Clin Obstet Gynecol 20:925 1977Gianopoulos G: Glucocorticoids and fetal lung development, in The Development of Responsiveness to Steroid Hormones, edited by Kaye AM, Kaye M, New York, Pergamon Press, 1978, p. 241D’ercole AJ, Underwood LE: Growth factors in fetal growth and development, in Fetal Endocrinology, edited by Now MI, Resko JA, New York, Academic Press, 1931, p. 155Young DA, Giddings S, Swonger A, Klurfeld G, Miller M: Interrelationships among the effects of glucocorticoids on carbohydrate, adenine nucleotide, RNA, and protein metabolism in rat thymous cells. Proc III Intl Cong Hormonal Steroid (Excerpta Med), p. 624Hallahan C, Young DA, Munck A: Time course of early events in the action of glucocorticoids on rat thymus cells in vitro: Synthesis and turnover of a hypothetical cortisolinduced protein inhibitor of glucose metabolism and of a presumed ribonucleic acid. J Biol Chem 248:2922 1973 PubMed ChemPort Munck A, Foley R: Kinetics of glucocorticoid receptor complexes in rat thymus cells. J Steroid Biochem 7:1117 1976 Article PubMed ISI ChemPort Foley JE, Jeffries M, Munck A: Rapid glucocorticoid effects on incorporation of lipid and protein precursors into rat thymus cell fractions. J Steroid Biochem 12:231 1981Ballard PL: Glucocorticoids and differentiation, in Glucocorticoid Hormone Action, edited by Baxter JD, Rousseau GG, New York, Springer 1979, p. 493Exton JH: Regulation of gluconeogenesis by glucocorticoids, in Glucocorticoid Hormone Action, edited by Baxter JD, Rousseau GG, New York, Springer 1979, p. 535Aperia A, Larsson L, Zetterstrom R: Hormonal induction of NaK ATPase in developing proximal tubular cells. Am J Physiol LF356 1981Igarashi Y, Aperia A, Larsson L, Zetterstrom R: Effect of betamethasone on NaKATPase activity and basal and lateral cell membranes in proximal tubular cells during early development. Experientia 40:489 1984Avner ED, Piesco NP, Sweeney WE Jr, Studnicki FM, Fetterman GH, Ellis D: Hydrocortisone cystic metanephric maldevelopment in serumfree organ culture. Lab Invest 50:208 1984 PubMed ISI ChemPort Avner ED, Sweeney WE Jr, Finegold DN, Piesco NP, Ellis D: Sodium ATPase activity mediates cyst formation in metanephric organ culture. Kidney Int 28:447 1985 PubMed ChemPort Marver D: Evidence of corticosteroid action along the nephron. Am J Physiol 245:F111 1984Lee SMK, Chekal MA, Katz AI: Corticosterone binding sites along the rat nephron. Am J Physiol 244:F504 1983Farman N, Vandewalle A, Bonvalet JP: Autoradiographic determination of dexamethasone binding sites along the rabbit nephron. Am J Physiol 244:F325 1983Lagenaur C, Sommer I, Schachner M: Subclass of astroglia in mouse cerebellum recognized by monoclonal antibody. Develop Biol 79:367 1980Taub M, Sato G: Growth of functional primary cultures of kidney epithelial cells in defined medium. J Cell Physiol 105:369 1980 Article PubMed ISI ChemPort Taub M: Growth of primary and established kidney cell cultures in serumfree media, in Methods of SerumFree Culture of Epithelial and Fiboblastic Cells, edited by Barnes DW, Sirbasku DA, Sato GH, New York, Alan R Liss, 1984, p. 3Scatchard G: The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660 1949 Article ChemPort Nordling S, Silja A: Fluorimetric microassay of DNA using a modified thiobarbituric acid assay. Anal Biochem 115:260 1981Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Che m 193:265 1951Yoda A, Yoda S: A new single preparation method for NaK ATPaserich membrane fragments. Anal Biochem 110:82 1981Philibert D: RU 38486: An original multifaceted antihormone in vivo, in Adrenal Steroid Antagonism, edited by Agarwal MK, Berlin, Walter de Gruyter Co, 1954, p. 77Cristofalo VJ, Rosner BA: Modulation of cell proliferation and senescence of WI38 asics store online cells by hydrocortisone. Fed Proc 38:1851 1979 PubMed ChemPort Cidlowski JA, Cidlowski NB: Glucocorticoid receptors and the cell cycle: Evidence that the accumulation of glucocorticoid receptors during the S phase of the cell cycle is dependent on ribonucleic acid and protein synthesis. Endocrinology 110:1653 1982Gupta C, Katsumata M, Goldman AS, Herold R, Piddington R: Glucocorticoid phospholipase A2inhibitory proteins mediate glucocorticoid teratogenecity in vitro. Proc Natl Acad Sci USA 81:1140 1984 Article PubMed ChemPort Baxter JD, Forsham PH: Tissue effects of glucocorticoid. Am J Med 53:573 1972 Article PubMed ISI ChemPort Ellis D, Turocy JF, Sweeney WE Jr, Avner ED: Partial characterization and ontogeny of renal cytosolic glucocorticoid receptors in mouse kidney. J Steroid Biochem 24:997 1986 Article PubMed ISI ChemPort Cidlowski JA, Cidlowski NB: Regulation of glucocorticoid receptors by glucocorticoids in cultured HeLa S 3 cells. Endocrinology 109:1975 1981Kontula K, Anderson LC, Paavonen T, Myllyla G, Teerenhovi L, Vuopio P: Glucocorticoid receptors and glucocorticoid sensitivity of human leukemic cells. Int J Cancer 26:177 1980Svec F, Rudis M: Glucocorticoids regulate the glucocorticoid receptor in the AtT20 cell. J Biol Chem 256:5984 1981 PubMed ChemPort Danielsen M, Stallcup MR: Down regulation of glucocorticoid receptors in mouse lymphoma cell variants. Mol Cell Biol 4:449 1984Rousseau GG, Schmit JP: Structureactivity relationships in glucocorticoids. I: Determination of receptor binding and biological activity. Biochemistry 8:911 1977Coty WA: Reversible dissociation of steroid hormone receptor complexes by mercurial reagents. J Biol Chem 255:8035 1980Banerji A, Kalimi M: Development of an [3H]glucocorticoid exchange assay in rat liver cytosol. Steroids 37:409 1981 Article PubMed ChemPort Rosner W, Polimeni T: An exchange assay for the cytoplasmic glucocorticoid receptor in the liver of the rat. Steroids 31:427 1978 Article PubMed ChemPort Bloom E, Matulich DT, Lan NC, Higgins SJ, Simmons SS, Baxter JD: Nuclear binding of glucocorticoid receptors: Relation between cytosol binding, activation, and the biological response. Steroid Biochem 12:175 1980Svec F, Yeakley J, Harison RW 3rd: The effect of temperature and binding kinetics on the competitive binding assay of steroid potency in intact AtT20 cells and cytosol. J Biol Chem 255:8573 1980Tornello S, Orti E, De nicola AF, Rainbow TC, Mcewen BS: Regulation of glucocorticoid receptors in brain by corticosterone treatment of adrenalectomized rats. Neuroendocrinology 35:411 1982 PubMed ChemPort Raaka BM, Samuels HH: The glucocorticoid receptor in GH1 cells. Evidence from dense amino acid labeling and whole cell studies of an equilibrium model explaining the influence of hormone on the intracellular distribution of receptor. Biol Chem 258:417 1983Lacroix A, Bonnard GD, Lippman ME: Modulation of glucocorticoid receptors by mitogenic stimuli, glucocorticoids, and retinoids in normal cultured human T cells. J Steroid Biochem 21:73 1984Sapolsky RM, Krey LC, Mc Ewen BS: Stress downregulates corticosterone receptors in a sitespecific manner in the brain. Endocrinology 114:287 1984Svec F: Glucocorticoid receptor regulation. Life Sci 36:2359 1985 Article PubMed ChemPort Jorgensen PL: Structure, function, and regulation of NaK ATPase in the kidney. Kidney Int 29:10 1986 PubMed Chignell CF, Titus E: Effect of adrenal steroids on Na+ and K+requiring adenosine triphosphatase from rat kidney. J Biol Chem 241:5083 1966Landon EJ, Jazab N, Forte L: Aldosterone and sodiumpotassiumdependent ATPase activity of rat kidney membranes. Am J Physiol 211:1050 1966Katz AI, Epstein FH: The rate of Na+K+ATPase in the reabsorption of sodium by the kidney. Clin Invest 46:1999 1967Hendler EO, Torretti J, Kupor L, Epstein FH: Effects of adrenalectomy and hormone replacement on Na+K+ATPase in renal tissue. Am J Physiol 222:754 1972Charney AN, Silva P, Besarab A, Epstein FH: Separate effects of aldosterone, DOCA, and methylprednisolone on renal NaKATPase. Am J Physiol 227:345 1974Fisher HS, Welt LG, Hayseltt JP: Dissociation of Na+K+ATPase specific activity and net reabsorption of sodium. Am J Physiol 228:1745 1975Rodriguez HJ, Sinha SK, Starling J, Klahr S: Regulation of renal Na+K+ATPase in the rat by adrenal steroids. Am J Physiol LF186 1981Sinha JK, Rodriguez HJ, Hogan WC, Klahr S: Mechanisms of activation of renal (Na+K+) ATPase in rat. Effects of acute and chronic administration of dexamethasone. Biochem Biophys Acta 641:20 1981Petty KJ, Kokko JP, Marver D: Secondary effect of aldosterone on NaK ATPase activity in the rabbit cortical collecting tubule. J Clin Invest 68:1514 1981 PubMed ISI ChemPort Mujais SK, Chekal MA, Jones WJ, Hayslett JP, Katz AJ: Regulation of renal NaK ATPase in the rat. Role of natural mineralo and glucocorticoid hormones. J Clin Invest 73:13 1984Rayson BM, Lowther SO: Steroid regulation of Na+K+ATPase: Differential sensitivities along with the nephron. Am J Physiol 246:F656 1984Garty H, Edelman IS, Lindemann B: Metabolic regulation of apical sodium permeability in toad urinary bladder in the presence and absence of aldosterone. Memb Biol 74:15 1983Katz AI: Distribution and function of classes of ATPase along the nephron. Kidney Int 29:21 1986Munck A, BrinckJohnsen T: Specific and nonspecific physiochemical interactions of glucocorticoids and related steroids with rat thymus asics outlet cells in vitro. J Biol Chem 243:5556 1968 PubMed ISI ChemPort Housley PR, Pratt WB: Direct demonstration of glucocorticoid phosphorylation by intact Lcells. J Biol Chem 258:4630 1983 PubMed ISI ChemPort Kurl RN, Jacob ST: Phosphorylation of purified glucocorticoid receptor from rat liver by an endogenous protein kinase. Biochem Biophys Res Comm 119:700 1984Grandics P, Miller A, Schmidt TJ, Litwack G: Phosphorylation in vivo of rat hepatic glucocorticoid receptor. Biochem Biophys Res Comm 120:59 1984Singh VB, Moudgil VK: Phosphorylation of rat liver glucocorticoid receptor. J Biol Chem 260:3684 1985 PubMed ISI ChemPort Granner DK, Beale EG: Regulation of the synthesis of tyrosine aminotransferase and phosphoenolpyruvate carboxykinase by glucocorticoid hormones, in Biochemical Actions of Hormones, edited by Litwack G, New York, Academic Press, Inc, Vol XII, 1985, p. 89Ishii DN, Pratt WB, Aronow L: Steadystate level of the specific glucocorticoid binding component in mouse fibroblasts. Biochemistry 11:3896 1972 Article PubMed ChemPort Rees AM, Bell PA: The involvement of receptor sulphydryl groups in the binding of steroids to the cystoplasmic glucocorticoid receptor from rat thymus. Biochem Biophys Acta 411:121 1975Joseph PK, Subrahmanyam K: Evaluation of the ratelimiting steps in the pathway of glucose metabolism in kidney cortex of normal, diabetic, and cortisonetreated and growth hormonetreated rats. Biochem J 128:1293 1972Guder WG, Schmidt U: The localization of gluconeogenesis in rat nephron: Determination of phosphoenolpyruvate carboxykinase in microdissected tubules. Hoppe Seylers Z Physiol Chem 355:273 1974Gunn JM, Hanson RW, Meyuhas O, Reshef L, Ballard FJ: Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat. Biochem J 150:195 1975Iynedjian PB, Ballard FJ, Hanson RW: The regulation of phosphoenolpyruvate carboxykinase synthesis in rat kidney cortex: The role of acidbase balance and glucocorticoids. J Biol Chem 250:5596 1975Moguilewsky M, Philibert D: RU 38486: Potent antiglucocorticoid activity correlated with strong binding asics outlet to the cytosolic glucocorticoid receptor followed by an impaired activation. J Steroid Biochem asics store online 20:271 1984 Article PubMed ISI ChemPort Lazar G, Agarwal MK: Physiological action and receptor binding of a newly synthesized and novel antiglucocorticoid. Biochem Biophys Res Commun 134:44 1986 asics store online.