Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-29T01:01:42.515Z Has data issue: false hasContentIssue false
  • English
  • Français

Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders

Published online by Cambridge University Press:  24 June 2014

Mario F Juruena ,
Anthony J Cleare ,
Moisés E Bauer  and
Carmine M Pariante
Mario F Juruena*
Affiliation:
Affective Disorders Unit, Federal University of Porto Alegre (FFFCMPA), Department of Psychiatry, Porto Alegre/RS, Brazil Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, Institute of Psychiatry, London, UK
Anthony J Cleare
Affiliation:
Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, Institute of Psychiatry, London, UK Affective Disorders Unit, Maudsley Hospital, London, UK
Moisés E Bauer
Affiliation:
FABIO and Institute for Biomedical Research, PUCRS, Porto Alegre/RS, Brazil
Carmine M Pariante
Affiliation:
Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, Institute of Psychiatry, London, UK Affective Disorders Unit, Maudsley Hospital, London, UK Section of Clinical Neuropharmacology, Division of Psychological Medicine, Institute of Psychiatry, London, UK
*
Mario Francisco Juruena, 103 Denmark Hill, London, SE5 8AZ, UK. Tel: +44 (0)207 848 5305; Fax: +44 (0)207 848 5408; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Changes in the hypothalamic–pituitary–adrenocortical (HPA) system are characteristic of depression, and in the majority of these patients these result in HPA axis hyperactivity. This is further supported by the reduced sensitivity to the inhibitory effects of the glucocorticoid, dexamethasone (DEX), on the production of adrenocorticotropic hormone (ACTH) and cortisol, during the DEX suppression test and the DEX-corticotropin-releasing hormone (DEX/CRH) test. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients. These studies have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRH in various brain regions postulated to be involved in the causality of depression. This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signaling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Hypotheses regarding the mechanism of these receptor changes involve non-steroid compounds that regulate GR function via second messenger pathways, such as cytokines and neurotransmitters. Moreover, we present recent evidence suggesting that membrane steroid transporters such as the multidrug resistance (MDR) p-glycoprotein, which regulate access of glucocorticoids to the brain, could be a fundamental target of antidepressant treatment. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.

Keywords

adrenocorticotropic hormoneantidepressantscorticotropin-releasing hormonecortisolcytokinesglucocorticoid receptorhypothalamic–pituitary–adrenal axismultiple drug resistance (MDR) p-glycoproteinneuroendocrinologypsychoneuroimmunology
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 6 , December 2003 , pp. 354 - 367
Copyright
Copyright © 2003 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

de Kloet, ER, Vreugdenhil, E, Oitzl, MS, Joels, M. Brain corticosteroid receptor balance in health and disease. Endocrinol Rev 1998;19: 269–301. Google ScholarPubMed
Pariante, CM, Miller, AH. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry 2001;49: 391–404.CrossRefGoogle ScholarPubMed
Gold, PW, Goodwin, FK, Chrousos, GP. Clinical and biochemical manifestation of depression: relation to the neurobiology of stress. N Engl J Med 1988;319: 413–420.CrossRefGoogle Scholar
Nemeroff, CB. The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry 1996;1: 336.Google ScholarPubMed
Kellner, M, Yehuda, R. Do panic disorder and posttraumatic stress disorder share a common psychoneuroendocrinology? Psychoneuroendocrinology 1999; 5: 485–504. CrossRefGoogle Scholar
Cleare, AJ, Blair, D, Chambers, S, Wessely, S. Urinary free cortisol in chronic fatigue syndrome. Am J Psychiatry 2001;158: 641–643.CrossRefGoogle ScholarPubMed
Cleare, AJ, Miell, J, Heap, Eet al. Hypothalamo- pituitary-adrenal axis function in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metabol 2001;86: 3545–3554. CrossRefGoogle ScholarPubMed
Gold, PW, Chrousos, GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002;7: 254–275.CrossRefGoogle ScholarPubMed
Holsboer, F, Barden, N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 1996;17: 187–205.CrossRefGoogle ScholarPubMed
Owens, MJ, Nemeroff, CB. The role of CRF in the pathophysiology of affective disorders: laboratory and clinical studies, Vol. 172.New York: John Wiley, 1993. Google ScholarPubMed
Carroll, BJ, Curtis, GC, Davies, BMet al. Urinary-free cortisol excretion in depression. J Psychol Med 1976;6: 43. CrossRefGoogle ScholarPubMed
Rubin, RT, Poland, RE, Lesser, IM, Winston, RA, Blodgett, ALN. Neuroendocrine aspects of primary endogenous depression. Arch General Psychiatry 1987; 44: 328–336. CrossRefGoogle ScholarPubMed
Sachar, EJ, Hellman, L, Roffwarg, HPet al. Disrupted 24-hour patterns of cortisol secretion in psychotic depression. Arch General Psychiatry 1973;28: 19. CrossRefGoogle ScholarPubMed
Carroll, J. Clinical applications of the dexamethasone suppression test for endogenous depression. Pharmacopsychiatry 1982;15: 19–24. CrossRefGoogle ScholarPubMed
Vale, W, Spiess, I, Rivier, C, Rivier, J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and p-endorphin. Science 1981;213: 1394–1397.CrossRefGoogle Scholar
Gold, PW, Loriaux, DL, Roy, Aet al. Responses to corticotrophin-releasing hormone in the hypoercortisolism of depression and Cushing's disease. N Engl J Med 1986;314: 1329–1335.CrossRefGoogle ScholarPubMed
Holsboer, F, Cerken, A, Von Bardeleben, Uet al. Human corticotropin-releasing hormone (CRH) in patients with depression, alcoholism and panic disorder. Biol Psychiatry 1986;21: 601–611.CrossRefGoogle Scholar
von Bardeleben, U, Holsboer, F. Cortisol response to a combined dexamethasone-hCRH challenge in patients with depression. J Neuroendocrinol 1989;1: 485–488. CrossRefGoogle Scholar
von Bardeleben, U, Holsboer, F. Effect of age upon the cortisol response to human CRH in depressed patients pretreated with dexamethasone. Biol Psychiatry 1991; 29: 1042–1050.CrossRefGoogle Scholar
Heuser, I, Yassouridis, A, Holsboer, F. The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatric Res 1994;28: 341–356. CrossRefGoogle Scholar
Meijer, OC, De Lange, EC M, Breimer, DD, De Boer, AC, Workel, JO, De Kloet, ER. Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdrlAP-glycoprotein knockout mice. Endocrinology 1998;139: 1789–1793.CrossRefGoogle ScholarPubMed
von Bardeleben, U, Holsboer, F, Stalla, GK, Muller, OA. Combined administration of human corticotropin-releasing factor and lysine vasopressin induces cortisol escape from dexamethasone suppression in healthy subjects. Life Sci 1985;37: 1613–1619.CrossRefGoogle ScholarPubMed
Orth, DN, Kovacs, WJ. The adrenal cortex. In. Wilson, JD, Foster, DW, Kronenberg, HM, Larsen, PR, eds. Williams textbook of endocrinology, 9th edn. Philadelphia: WB Saunders, 1998: 517–664. Google Scholar
Pariante, CM, Papadopoulos, AS, Poon, Let al. A novel prednisolone suppression test for the hypothalamic-pituitary-adrenal axis. Biol Psychiatry 2002;51: 922–930.CrossRefGoogle ScholarPubMed
Karssen, AM, Meijer, OC, Van Der Sandt, ICet al. Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain. Endocrinology 2001;142: 2686–2694.CrossRefGoogle Scholar
Nemeroff, CB, Widerlov, E, Bissette, Cet al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984;226: 1342–1344.CrossRefGoogle ScholarPubMed
Nemeroff, CB, Owens, MJ, Bissette, G, Andorn, AC, Stanley, M. Reduced corticotropin-releasing factor (CRF) binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988;45: 377–379.CrossRefGoogle ScholarPubMed
Raadsheer, FC, Hoogendijk, WIG, Stam, FC, Tilders, FHJ, Swaab, DF. Increased numbers of corticotropinreleasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994;60: 433–436. CrossRefGoogle ScholarPubMed
de Bellis, MD, Cold, PW, Ceracioti, TD Jr,Listwak, SI, Kling, MA. Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. Am J Psychiatry 1993;150: 656–657.Google ScholarPubMed
Reul, JM, De Kloet, ER. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 1985;117: 2505–2511.CrossRefGoogle ScholarPubMed
Miller, AH, Spencer, RL, Pulera, M, Kang, S, McEwen, BS, Stein, M. Adrenal steroid receptor activation in rat brain and pituitary following dexamethasone. Implications for the dexamethasone suppression test. Biol Psychiatry 1992; 32: 850–869.CrossRefGoogle ScholarPubMed
Young, EA, Haskett, RF, Murphy. Weinberg, V, Watson, SI, Akil, H. Loss of glucocorticoid fast feedback in depression. Arch Gen Psychiatry 1991;48: 693–699.CrossRefGoogle ScholarPubMed
Ribeiro, SCM, Tandon, R, Grunhaus, L, Greden, JF. The DST as a predictor of outcome in depression: a meta-analysis. Am J Psychiatry 1993;150: 1618–1629.Google ScholarPubMed
Zobel, AW, Yassouridis, A, Frieboes, RM, Holsboer, F. Prediction of medium-term outcome by cortisol response to the combined dexamethasone-CRH test in patients with remitted depression. Am J Psychiatry 1999;156: 949–951.CrossRefGoogle Scholar
Zobel, AW, Nickel, T, Sonntag, A, Uhr, M, Holsboer, F, Ising, M. Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression a prospective study. J Psych Res 2001;35: 83–94. CrossRefGoogle ScholarPubMed
Spencer, RL, Kim, PJ, Kalman, BA, Cole, MA. Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor-dependent regulation of hypothalamic-pituitary-adrenal axis activity. Endocrinology 1998; 139: 2718–2726.CrossRefGoogle ScholarPubMed
Pratt, WB. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 1993;268: 21455–21458.CrossRefGoogle ScholarPubMed
Guiochon-Mantel, A, Delabre, K, Lescop, P, Milgrom, E. Intracellular traffic of steroid hormone receptors. J Steroid Biochem Mol Biol 1996;56: 3–9.CrossRefGoogle ScholarPubMed
Modell, S, Yassouridis, A, Huber, I, Holsboer, F. Corticosteroid receptor function is decreased in depressed patients. Neuroendocrinology 1997;65: 216–222.CrossRefGoogle ScholarPubMed
Murphy, BE P. Treatment of major depression with steroid suppressive drugs. I. Steroid Biochem Mol Biol 1991;39: 239–244. CrossRefGoogle Scholar
Gametchu, B. Glucocorticoid receptor-like antigen in lymphoma cell membranes: correlation to cell lysis. Science 1987;236: 456–461.CrossRefGoogle ScholarPubMed
Webster, MJ, O'Grady, J, Orthmann, C, Weickert, C. Decreased glucocorticoid receptor mRNA levels in individuals with depression, bipolar disorder and Schizophrenia. Schizophr Res 2000;41: 111. CrossRefGoogle Scholar
Cotter, D, Pariante, CM. Stress on the brain. Beyond the developmental hypothesis of schizophrenia? Br J Psychiatry 2002; 181: 363–365.CrossRefGoogle Scholar
Lopez, JF, Chalmers, DT, Little, KI, Watson, SJ. Regulation of serotonin 1A, glucocorticoid and mineralocorticoid receptor in rat and human hippocampus. Implications for the neurobiology of depression. Biol Psychiatry 1998;43: 547–573.CrossRefGoogle ScholarPubMed
Bauer, M, Vedhara, K, Perks, P, Wilcock, G, Lightman, S, Shanks, N. Chronic stress in caregivers of dementia patients is associated with reduced lymphocyte sensitivity to glucocorticoids. J Neuroimmunol 2000; 103: 84–92.CrossRefGoogle ScholarPubMed
Kok, F, Heijnen, C, Bruijn, J, Westenberg, H, Ree, J. Immunoglobulin production in vitro in major depression: a pilot study on the modulating action of endogenous cortisol. Biol Psychiatry 1995;38: 217–226.CrossRefGoogle ScholarPubMed
Bauer, ME, Papadopoulus, A, Poon, Let al. Altered glucocorticoid immunoregulation in treatment resistant depression. Psychoneuroendocrinology 2003;28: 49–65.CrossRefGoogle ScholarPubMed
Bauer, M, Papadopoulos, A, Poon, L, Perks, P, Lightman, S, Checkley, S, Shanks, N. Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment resistant major depression. Psychiatr Res 2002; 113: 1–15. CrossRefGoogle Scholar
Asnis, GM, Haibreich, U, Ryan, NDet al. The relationship of the dexamethasone suppression test (1 mg and 2 mg) to basal plasma cortisol levels in endogenous depression. Psychoneuroendocrinology 1987;12: 295–301.CrossRefGoogle ScholarPubMed
Miller, Ah, Sastry, G, Speranza, AJ Jret al. Lack of association between cortisol hypersecretion and nonsuppression on the DST in patients with Alzheimer's disease. Am J Psychiatry 1994;151: 267–270.Google ScholarPubMed
Cotter, P, Mulligan, O, Landau, S, Papadopoulos, A, Lightman, S, Checkley, S. Vasoconstrictor response to topical beclomethasone in major depression. Psychoneuroendocrinology 2002;27: 475–487.CrossRefGoogle ScholarPubMed
Maguire, TM, Thakore, J, Dinan, TG, Hopwood, S, Breen, KC. Plasma sialyltransferase levels in psychiatric disorders as a possible indicator of HPA function. Biol Psychiatry 1997;41: 1131–1136.CrossRefGoogle Scholar
Thakore, JH, Richards, PJ, Reznek, RH, Martin, A, Dinan, TG. Increased intra-abdominal fat deposition in patients with major depression illness as measured by computed tomography. Biol Psychiatry 1997;41: 1140–1142.CrossRefGoogle ScholarPubMed
Schweiger, U, Deuschle, M, Korner, Aet al. Low lumbar bone mineral density in patients with major depression. Am J Psychiatry 1994;151: 1691–1693.Google ScholarPubMed
Michelson, D, Stratakis, C, Hill, Let al. Bone mineral density in women with depression. N Engl J Med 1996;335: 1176–1181.CrossRefGoogle ScholarPubMed
O'Malley, BW, Schrader, WT, Mani, Set al. An alternative ligand independent pathway for activation of steroid receptors. Recent Prog Horm Res 1995; 50: 333–347.Google ScholarPubMed
Miller, Ah, Pariante, CM, Pearce, BD. Effects of cytokines on glucocorticoid receptor expression and function: glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 1999;461: 107–116.CrossRefGoogle ScholarPubMed
Pariante, CM, Pearce, BD, Pisell, TL, Sanchez, CI, Po, C, Su, C, Miller, AH. The proinflammatory cytokine, interleukin-1 alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 1999;140: 4359–4366.CrossRefGoogle ScholarPubMed
Rangarajan, PN, Umesono, K, Evans, RM. Modulation of glucocorticoid receptor function by protein kinase A. Mol Endocrinol 1992;6: 1451–1457.Google ScholarPubMed
Avissar, S, Nechamkin, Y, Roitman, G, Schreiber, G. Reduced G protein functions and immunoreactive levels in mononuclear leukocyts of patients with depression. Am J Psychiatry 1997;154: 211–217.Google Scholar
Shelton, RC, Manier, Dh, Sulser, F. cAMP-dependent protein kinase activity in major depression. Am J Psychiatry 1996;153: 1037–1042.Google ScholarPubMed
Castro, M, Elliot, S, Kino, Tet al. The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGC-beta): tissue levels, mechanism of action, and potential physiologic role. Mol Med 1996;2: 597–607.CrossRefGoogle Scholar
Bronnegard, M, Stierna, P, Marcus, C. Glucocorticoid resistant syndromes – molecular basis and clinical presentations. J Neuroendocrinol 1996;8: 405–415.CrossRefGoogle ScholarPubMed
Korf, J, Klein, HC, Versijpt, J, Den Boer, JA, Ter Horst, GJ. Considering depression as a consequence of activation of the inflammatory response system. Acta Neuropsychiatrica 2002;14: 1–10. CrossRefGoogle ScholarPubMed
Wessely, S, Pariante, CM. Fatigue, depression and chronic hepatitis C infection. Psychol Med 2002;32: 1–10.CrossRefGoogle ScholarPubMed
Pariante, CM, Landau, S, Carpiniello, B. Interferon-alpha-induced psychiatric adverse effects in patients with chronic viral hepatitis and a psychiatric diagnosis: a prospective, controlled study. N Engl J Med 2002; 347: 148–149.CrossRefGoogle Scholar
Pariante, CM, Orru', MG, Baita, A, Farci, MG, Carpiniello, B. Treatment with interferon-alpha in patients with chronic hepatitis and mood or anxiety disorders. The Lancet 1999;354: 131–132. CrossRefGoogle ScholarPubMed
Maes, M, Scharpe, S, Meltzer, HYet al. Relationship between interleukin-6 activity, acute phase proteins, and the function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatr Res 1993;49: 11–27. CrossRefGoogle ScholarPubMed
Maes, M, Meester, I, Verkerk, Ret al. Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers. Psychoneuroendocrinology 1997; 22: 65–78.CrossRefGoogle ScholarPubMed
Kubera, M, Van Bockstaele, D, Maes, M. Leukocyte subsets in treatment-resistant major depression. Pol J Pharmac 1999;51: 547–549. Google ScholarPubMed
Pariante, CM. Cytokines and depression. Perspectives Depression 2001;9: 1–5. Google Scholar
Zhou, D, Kusnecov, AW, Shurin, MR, Depaoli, M, Rabin, BS. Exposure to physical and psychological stressors elevates plasma interleukin 6. relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinol 1993;6: 2523–2530. CrossRefGoogle Scholar
Zaharia, M, Ravindran, A, Griffiths, J, Merali, Z, Anisman, H. Lymphocyte proliferation among major depressive and dysthymic patients with typical or atypical features. J Affect Disord 2000;58: 1–10.CrossRefGoogle ScholarPubMed
Maddock, C, Pariante, CM. How does stress affect you? An overview of stress, immunity, depression and disease. Epidemiologia e Psichiatria Sociale 2001;10: 153–162.CrossRefGoogle Scholar
Nebbia, G, Pariante, CM, Kerwin, RW. The molecular mechanisms by which the proinflammatory cytokine, interleukin-1, influences the glucocorticoid receptor: relevance for glucocorticoid resistance and major depression. Ital J Psychiatry Behav Sci 2000;10: 10–16. Google Scholar
Pariante, CM, Makoff, A, Lovestone, Set al. Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters. Br J Pharmacol 2001;134: 1335–1343.CrossRefGoogle ScholarPubMed
Pariante, CM, Pearce, BD, Pisell, TL, Owens, MJ, Miller, Ah. Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Mol Pharmacol 1997;52: 571–581.CrossRefGoogle ScholarPubMed
Holsboer, F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000;23: 477–501.CrossRefGoogle ScholarPubMed
Barden, N. Regulation of corticosteroids receptor gene expression in depression and antidepressant action. J Psychiatry Neurosci 1999;24: 25–39.Google ScholarPubMed
McQuade, R, Young, Ah. Future therapeutic targets in mood disorders: the glucocorticoid receptor. Br J Psychiatry 2000;177: 390–395.CrossRefGoogle ScholarPubMed
Budziszewska, B, Jaworska-Feil, L, Kajta, M, Lason, W. Antidepressant drugs inhibit glucocorticoid receptor mediated gene transcription-a possible mechanism. Br J Pharmacol 2000;130: 1385–1393.CrossRefGoogle ScholarPubMed
Pariante, CM, Pearce, BD, Pisell, TL, Su, C, Miller, AH. The steroid receptor antagonists, RU486 and RU40555, activate glucocorticoid receptor translocation and are not excreted by the steroid hormone transporter in L929 cells. J Endocrinol 2001;169: 309–320.CrossRefGoogle Scholar
Krishna, R, Mayer, LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci 2000;11: 265–283.CrossRefGoogle ScholarPubMed
Ueda, K, Okamura, N, Hirai, Met al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 1992; 267: 24 248–24 252.CrossRefGoogle Scholar
de Kloet, ER, Meijer, OC, Vreugdenhil, E, Joels, M. The Yin and Yang of nuclear receptors: symposium on nuclear receptors in brain, Oegstgeest, The Netherlands, 13–14 April 2000. Trends Endocrinol Metab 2000; 11: 245–248.CrossRefGoogle ScholarPubMed
Bourgeois, S, Gruol, DJ, Newby, RF, Rajah, FM. Expression of an mdr gene is associated with a new form of resistance to dexamethasone-induced apoptosis. Mol Endocrinol 1993;7: 840–851.Google ScholarPubMed
Varga, A, Nugel, H, Baehr, Ret al. Reversal of multidrug resistance by amitriptyline in vitro. Anticancer Res 1996;16: 209–212.Google ScholarPubMed
Merry, S, Hamilton, TG, Flanigan, P, Freshney, RI, Kaye, SB. Circumvention of pleiotropic drug resistance in subcutaneous tumours in vivo with verapamil and clomipramine. Eur J Cancer 1991;27: 31–34.CrossRefGoogle ScholarPubMed
Szabo, D, Szabo, G Jr, Ocsovszki, I, Aszalos, A, Molnar, J. Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cell ex-vivo. Cancer Lett 1999;139: 115–119.CrossRefGoogle ScholarPubMed
Uhr, M, Steckler, T, Yassouridis, A, Holsboer, F. Penetration of amitriptyline, but not fluoxetine, into brain is enhanced in mice with blood–brain barrier deficiency due to MDR1a p-glycoprotein gene disruption. Neuropsychopharmacology 2000;22: 380–387.CrossRefGoogle Scholar
Kralli, A, Yamamoto, KR. An FK506-sensitive transporter selectively decreases intracellular levels and potency of steroid hormones. J Biol Chem 1996;271: 17152–17156.CrossRefGoogle ScholarPubMed
Marsaud, V, Mercier-Bodard, C, Fortin, D, Le Bihan, S, Renoir, J-M. Dexamethasone and triamcinolone acetonide accumulation in mouse fibroblasts is differently modulated by the immunosuppressants cyclosporin A, FK506, rapamycin and their analogues, as well as by other p-glycoprotein ligands. J Steroid Biochem Molec Biol 1998;66: 11–25.CrossRefGoogle ScholarPubMed
Medh, RD, Lay, Rh, Schmidt, TJ. Agonist-speciffic modulation of glucocorticoid receptor-mediated transcription by immunosuppressants. Mol Cell Endocrinol 1998;138: 11–23.CrossRefGoogle ScholarPubMed
Przegalinski, E, Budziszewska, B, Siwanowicz, J, Jaworska, L. The effect of repeated combined treatment with nifedipine and antidepressant drugs or electroconvulsive shock on the hippocampal corticosteroid receptors in rats. Neuropharmacology 1993;32: 1397–1400.CrossRefGoogle ScholarPubMed
Lowy, M, Gormley, G, Reder, A, Meltzer, H. Immune function, glucocorticoid receptor regulation, and depression. In: Miller, A, ed. Depressive disorders and immunity. Washington, DC: American Psychiatric Press, 1989: 107–133. Google Scholar
Moalli, P, Rosen, S. Glucocorticoid receptors and resistance to glucocorticoids in hematologia malignancies. Leuk Lymph 1994;15: 363–374. CrossRefGoogle Scholar
Cypcar, D, Busse, W. Steroid-resistant asthma. J Allergy Clin Immunol 1993;92: 362–372.CrossRefGoogle ScholarPubMed
Hennebold, J, Daynes, R. Microenvironmental control of glucocorticoid functions in immune regulation. In: Rook, G, Lightman, S, eds. Steroid hormones and the T-cell cytokine profile. London: Springer-Verlag, 1997: 101–134. CrossRefGoogle Scholar
Adcock, I, Lane, S, Brown, C, Peters, M, Lee, T, Barnes, P. Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 1995;154: 3500–3505.CrossRefGoogle ScholarPubMed
Rosner, W. Plasma steroid-binding proteins. Endocr Metab Clin North Amer 1991;20: 697–720. CrossRefGoogle ScholarPubMed
Pepin, MC, Beaulieu, S, Barden, N. Antidepressants regulate glucocorticoid receptor messenger RNA concentrations in primary neuronal cultures. Brain Res Mol Brain Res 1989;6: 77–83.CrossRefGoogle ScholarPubMed
Peiffer, A, Veilleux, S, Barden, N. Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain. Psychoneuroendocrinology 1991;16: 505–515.CrossRefGoogle ScholarPubMed
Seckl, JR, Fink, G. Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo. Neuroendocrinology 1992;55: 621–626.CrossRefGoogle ScholarPubMed
Pepin, MC, Pothier, F, Barden, N. Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression. Mol Pharmacol 1992;42: 991–995.Google Scholar
Pepin, MC, Govindan, MV, Barden, N. Increased glucocorticoid receptor gene promoter activity after antidepressant treatment. Mol Pharmacol 1992;41: 1016–1022.Google ScholarPubMed
Budziszewska, B, Siwanowicz, J, Przegalinski, E. The effect of chronic treatment with antidepressant drugs on the corticosteroid receptor levels in the rat hippocampus. Pol J Pharmacol 1994;46: 147–152.Google ScholarPubMed
Rossby, SP, Nalepa, I, Huang, Met al. Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant. Brain Res 1995;687: 79–82.CrossRefGoogle ScholarPubMed
Eiring, A, Sulser, F. Increased synaptic availability of norepinephrine following desipramine is not essential for increases in GR mRNA. J Neural Transm 1997; 104: 1255–1258.CrossRefGoogle Scholar
Reul, JM, Stec, I, Soder, M, Holsboer, F. Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system. Endocrinology 1993; 133: 312–320.CrossRefGoogle ScholarPubMed
Peeters, BWMM, Van Der Heijden, R, Gubbels, DG, Vanderheyden, PML. Effects of chronic antidepressant treatment on the hypothaiamic-pituitary-adrenal axis of Wistar rats. Ann NY Acad Sci 1994;746: 449–452.CrossRefGoogle ScholarPubMed
Kitayama, I, Janson, AM, Cintra, Aet al. Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. J Neural Transm 1988;73: 191–203.CrossRefGoogle ScholarPubMed
Brady, LS, Cold, PW, Herkenham, M, Lynn, AB, Whitfield, HJR. The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain;therapeutic implications. Brain Res 1992; 572: 117–125.CrossRefGoogle ScholarPubMed
Brady, LS, Whitfield, HJR, Fox, RJ, Gold, PW, Herkenham, M. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. J Clin Invest 1991; 87: 831–837.CrossRefGoogle ScholarPubMed
Reul, JMHM, Labeur, MS, Grigoriadis, DE, De Souza, EB, Holsboer, F. Hypothalamic-pituitary-adrenocortical axis changes in the rat after long-term treatment with the reversible monoamine oxidase-A inhibitor moclobemide. Neuroendocrinology 1994;60: 509–519.CrossRefGoogle ScholarPubMed