This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Emptoz-Bonneton, A. Articles by Pugeat, M. Search for Related Content PubMed PubMed Citation Articles by Emptoz-Bonneton, A. Articles by Pugeat, M.

Corticosteroid-Binding Globulin Synthesis Regulation by Cytokines and Glucocorticoids in Human Hepatoblastoma-Derived (HepG2) Cells¹

Hospices Civils de Lyon, Laboratoire de la Clinique Endocrinologique, Hôpital de l’Antiquaille, 69321 Lyon, France; and INSERM U-329, Hôpital Debrousse, 69005 Lyon, France

Address all correspondence and requests for reprints to: Prof. Michel Pugeat, Clinique Endocrinologique, Hôpital de l’Antiquaille, 1 rue de l’Antiquaille, 69321 Lyon Cedex, France.

Plasma corticosteroid-binding globulin (CBG) concentrations decrease dramatically in patients with septic shock or burn injury. This decrease suggests that mediators of the acute phase response, such as cytokines and glucocorticoid hormones, might influence clearance as well as liver synthesis of CBG in humans. The present study investigated the effects of interleukin-6 (IL-6), IL-1ß, and dexamethasone on CBG synthesis by a clone of human hepatoblastoma-derived (HepG2) cell line.

In culture medium from HepG2 cells, the immunoconcentration of CBG and the levels of CBG messenger ribonucleic acid (mRNA) were dose dependently decreased in the presence of IL-6 concentrations ranging from 0.1–10 ng/mL. The percent decrease in CBG immunoconcentration was quantitatively similar to the percent decrease in CBG mRNA levels (29 ± 6% and 39 ± 15%, respectively, of control values). In contrast, and as expected, IL-6 dose dependently increased the mRNA levels (164 ± 22% of control values) of ₁-antitrypsin, a positive acute phase protein, but did not affect the immunoconcentration of sex hormone-binding globulin, another liver protein.

Dexamethasone alone did not significantly affect CBG secretion or mRNA levels, but did dose-dependently increase tyrosine aminotransferase mRNA levels, which increased to 252 ± 16% of the control values. However, in combination with IL-6, dexamethasone had a significant additive effect on IL-6 inhibition of CBG secretion and mRNAs in HepG2 cells.

IL-1ß dose-dependently stimulated CBG secretion (156 ± 10% of control values) with no significant effect on CBG mRNA levels. In addition, IL-1ß significantly decreased the inhibitory effect of IL-6 on CBG secretion, but had no effect on the inhibitory effect of IL-6 on CBG mRNA levels. These results suggest that IL-1ß acts on the posttranslation processing and/or secretion mechanisms of CBG in HepG2 cells.

Together, the present results strongly support the hypothesis that the decrease in plasma CBG concentrations is associated with the increase in IL-6 and glucocorticoid levels reported in patients with septic shock and burn injury.

This article has been cited by other articles:

				K. Wingenfeld, C. Heim, I. Schmidt, D. Wagner, G. Meinlschmidt, and D. H. Hellhammer HPA Axis Reactivity and Lymphocyte Glucocorticoid Sensitivity in Fibromyalgia Syndrome and Chronic Pelvic Pain Psychosom Med, January 1, 2008; 70(1): 65 - 72. [Abstract] [Full Text] [PDF]

				R H Straub, P Sarzi-Puttini, F Atzeni, F Buttgereit, M Carrabba, and M Cutolo Anti-tumour necrosis factor antibody treatment does not change serum levels of cortisol binding globulin in patients with rheumatoid arthritis but it increases androstenedione relative to cortisol Ann Rheum Dis, September 1, 2005; 64(9): 1353 - 1356. [Abstract] [Full Text] [PDF]

				M. D'Elia, J. Patenaude, C. Hamelin, D. R. Garrel, and J. Bernier Corticosterone binding globulin regulation and thymus changes after thermal injury in mice Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E852 - E860. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Real and W. Ricart Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome Endocr. Rev., June 1, 2003; 24(3): 278 - 301. [Abstract] [Full Text] [PDF]

				J.-M. Fernandez-Real, M. Pugeat, M. Grasa, M. Broch, J. Vendrell, J. Brun, and W. Ricart Serum Corticosteroid-Binding Globulin Concentration and Insulin Resistance Syndrome: A Population Study J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4686 - 4690. [Abstract] [Full Text] [PDF]

				D. J. Torpy, A. W. Bachmann, J. E. Grice, S. P. Fitzgerald, P. J. Phillips, J. A. Whitworth, and R. V. Jackson Familial Corticosteroid-Binding Globulin Deficiency Due to a Novel Null Mutation: Association with Fatigue and Relative Hypotension J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3692 - 3700. [Abstract] [Full Text] [PDF]

				F.J.L. Kaplan, N.S. Levitt, and S.G. Soule Primary hypoadrenalism assessed by the 1 {micro}g ACTH test in hospitalized patients with active pulmonary tuberculosis QJM, September 1, 2000; 93(9): 603 - 609. [Abstract] [Full Text] [PDF]

				C. Tsigos, I. Kyrou, G. P. Chrousos, and D. A. Papanicolaou Prolonged Suppression of Corticosteroid-Binding Globulin by Recombinant Human Interleukin-6 in Man J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3379 - 3379. [Full Text]