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Effects of experimentally induced hyperthyroidism on central hypothalamic–pituitary–adrenal axis function in rats: in vitro and in situ studies

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An Erratum to this article was published on 13 January 2013

Abstract

Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic–pituitary–adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague–Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

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References

  1. Kamilaris TC, DeBold CR, Johnson EO, Mamalaki E, Listwak SJ, Calogero AE, Kalogeras KT, Gold PW, Orth DN (1991) Effects of short and long duration hypothyroidism and hyperthyroidism on the plasma adrenocorticotropin and corticosterone responses to ovine corticotropin-releasing hormone in rats. Endocrinology 128:2567–2576

    Article  PubMed  CAS  Google Scholar 

  2. Tsatsoulis A, Johnson EO, Kalogera CH, Seferiadis K, Tsolas O (2000) The effect of thyrotoxicosis on adrenocortical reserve. Eur J Endocrinol 42:231–235

    Article  Google Scholar 

  3. Johnson EO, Kamilaris TC, Calogero AE, Gold PW, Chrousos GP (2005) Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis. Eur J Endocrinol 153:177–185

    Article  PubMed  CAS  Google Scholar 

  4. Dallman MF, Akana SK, Cascio CS, Darlington DN, Jacobson L, Levin N (1987) Regulation of ACTH secretion: variations on a theme of B. Recent Prog Horm Res 43:113–167

    PubMed  CAS  Google Scholar 

  5. Drouin J, Chamberland M, Carron J, Jeannotte L, Nemer M (1985) Structure of the rat pro-opiomelanocortic (POMC) gene. FEBS 193:54–58

    Article  CAS  Google Scholar 

  6. Ivell R, Richter D (1984) Structure and comparison of the oxytocin and vasopressin genes from rat. Proc Natl Acad Sci USA 81:2006–2010

    Article  PubMed  CAS  Google Scholar 

  7. Jingami H, Mizuno N, Takahashi H, Shibahara S, Furutani Y, Imura H, Numa S (1985) Cloning and sequence analysis of cDNA for rat corticotropin-releasing factor precursor. FEBS 191:63–66

    Article  CAS  Google Scholar 

  8. Lightman SE, Young WS (1987) Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor mRNA stimulation in the rat. J Physiol 394:23–39

    PubMed  CAS  Google Scholar 

  9. Lightman SL, Young WS III (1989) Influence of steroids on the hypothalamic corticotropin-releasing factor and preproenkephalin mRNA responses to stress. Proc Natl Acad Sci USA 86:4306–4310

    Article  PubMed  CAS  Google Scholar 

  10. Young WS (1989) In situ hybridization histochemical detection of neuropeptide mRNA using DNA and RNA probes. Methods Enzymol 168:702–709

    Article  PubMed  CAS  Google Scholar 

  11. Calogero AE, Kamilaris TC, Gomez MT, Johnson EO, Tartaglia ME, Gold PW, Chrousos GP (1989) The muscarinic cholinergic agonist arecoline stimulates the rat hypothalmic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism. Endocrinology 125:2445–2453

    Article  PubMed  CAS  Google Scholar 

  12. Calogero AE, Bagdy G, Szemeredi K, Tartaglia ME, Gold PW, Chrousos GP (1990) Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic-pituitary-adrenal axis in the rat. Endocrinology 126:1888–1894

    Article  PubMed  CAS  Google Scholar 

  13. Calogero AE, Kamilaris TC, Bernardini R, Johnson EO, Chrousos GP, Gold PW (1990) Effects of peripheral benzodiazepine receptor ligands on hypothalmic-pituitary-adrenal axis function in the rat. J Pharmacol Exp Therap 253:729–737

    CAS  Google Scholar 

  14. Bagdy G, Calogero AE, Szemeredi K, Gomez MT, Murphy DL, Chrousos GP, Gold PW (1990) b-Endorphin responses to different serotonin agonists: involvement of corticotropin-releasing hormone, vasopressin and direct pituitary action. Brain Res 537:227–232

    Article  PubMed  CAS  Google Scholar 

  15. Johnson EO, Kamilaris TC, Chrousos GP, Gold PW (1992) Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci Biobehav Rev 16:115–130

    Article  PubMed  CAS  Google Scholar 

  16. Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Molecular Psych 7:254–275

    Article  CAS  Google Scholar 

  17. Boler RK, Moore NA (1982) Depression of adrenocortical function by pharmacologic doses of thyroxine in intact and unilaterally adrenalectomized rats. Horm Res 16:209–218

    Article  PubMed  CAS  Google Scholar 

  18. Breuner CW, ORchinik M (2002) Beyond carrier proteins: plasma binding proteins as mediators of corticosteroid action in vertebrates. J Endocr 175:99–112

    Article  PubMed  CAS  Google Scholar 

  19. D’Agostino J, Henning SJ (1982) Role of thyrozine in coordinate control of corticosterone and CBG in postnatal development. Am J Physiol 242:E33–E39

    PubMed  Google Scholar 

  20. Smith CL, Hammond GL (1992) Hormonal regulation of corticosteroid-binding globulin biosynthesis in the male rat. Endocrinology 130:2245–2251

    Article  PubMed  CAS  Google Scholar 

  21. Wardlaw SL, McCarthy KC, Conwell IR (1998) Glucocorticoid regulation of hypothalamic proopiomelanocortin. J Neuroendocrinology 67:51–57

    Article  CAS  Google Scholar 

  22. Grigorakis SI, Anastasiou E, Dai K, Souvatzoglou A, Alevizaki M (2000) Three mRNA transcripts of the proopiomelanocortin gene in human placenta at erm. Eur J Endocrin 142:533–536

    Article  CAS  Google Scholar 

  23. Pritchard LE, Turnbull AV, White A (2002) Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol 172:411–421

    Article  PubMed  CAS  Google Scholar 

  24. Pinnock SB, Herbert J (2001) Corticosterone differentially modulates expression of corticotropin releasing factor and arginine vasopressin mRNA in the hypothalamic paraventricular nucleus following either acute or repeated restraint stress. Eur J Neurosci 13:576–584

    Article  PubMed  CAS  Google Scholar 

  25. Albeck DS, McKittrick CR, Blanchard DC, Blanchard RJ, Nikulina J, McEwen BS, Sakai RR (1997) Chronic social stress alters levels of corticotropin-releasing factor and arginine vasopressin mRNA in rat brain. J Neurosci 17:4895–4903

    PubMed  CAS  Google Scholar 

  26. Mogulkoc R, Baltaci AK (2006) Influences of isotonic, hypertonic and hypovolemic treamtents on vasopressin response and fluid-electrolyte balance in l-thyroxine-induced hyperthyroid rat. Life Sci 79:817–821

    Article  PubMed  CAS  Google Scholar 

  27. Dakine N, Oliver C, Grino M (2000) Thyroixine modulates corticotropin-releasing factor but not arginene vasopressin gene expression in the hypothalamic-paraventricular nucleus of the developing rat. J Neuroendocrinol 12:774–783

    Article  PubMed  CAS  Google Scholar 

  28. Lizcano F, Salvador J (2008) Effects of different treatments for hyperthyroidism on the hypothalamic-pituitary-adrenal axis. Clin Exp Pharm Phys 35:1085–1090

    Article  CAS  Google Scholar 

  29. Lizcano F, Salvador Rodriguez J (2011) Thyroid hormone therapy modulates hypothalamo-pituitary-adrenal axis. Endocrine J 58:137–142

    Article  CAS  Google Scholar 

  30. Mathews SG, Challis JR (1997) CRH and AVP-induced changes in synthesis and release of ACTH from the ovine fetal pituitary in vitro: negative influences of cortisol. Endocrine 6:293–300

    Article  Google Scholar 

  31. Gallagher TF, Hellman L, Finkelstein J, Yoshida K, Weitzman ED, Roffward HD, Fukushima DK (1972) Hyperthyroidism and cortisol secretion in man. J Clin Endocrinol Metab 34:919–927

    Article  PubMed  CAS  Google Scholar 

  32. Kawaguch M, Iwata S, Kamiya Y, Hayakawa F, Fujii T, Ito J, Sakuma N, Fujinami T (1992) Thyroid storm associated with probable subclinical hypoadrenocortiscism in an elderly woman. Intern Med 31:1236–1238

    Article  Google Scholar 

  33. Mazzaferri MEZ, Skillman TG (1969) Thyroid storm. Arch Intern Med 124:684–690

    Article  PubMed  CAS  Google Scholar 

  34. Ingbar SH (1966) Management of emergencies. IX. Thyroid storm. N Engl J Med 274:1252–1254

    Article  PubMed  CAS  Google Scholar 

  35. Burch HB, Wartofsky L (1993) Life-threatening thyrotoxicosis. Endocrinol Metab Clin North Am 22:263–277

    PubMed  CAS  Google Scholar 

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Acknowledgments

Material for the rat TSH RIA was provided by the National Hormone and Pituitary Program.

Conflict of interest

No major sources of funding were received for the research reported and thus, there is no conflict of interest that would prejudice the impartiality of the results presented.

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, University of Athens, 75 Mikras Asias Str., 11527, Goudi, Athens, Greece

    Elizabeth O. Johnson

  2. Section of Endocrinology, Andrology and Internal Medicine, Department of Biomedical Sciences, University of Catania, Ospedale Garibaldi, Piazza S Maria de Gesu, Catania, Italy

    Aldo E. Calogero

  3. Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, Greece

    Maria Konstandi

  4. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA

    Themis C. Kamilaris

  5. Section of Endocrinology, Andrology and Internal Medicine, Department of Internal Medicine and Systemic Disease, University of Catania, Catania, Italy

    Sandro La Vignera

  6. 1st Department of Pediatrics, School of Medicine, University of Athens, Athens, Greece

    George P. Chrousos

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  1. Elizabeth O. Johnson
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  2. Aldo E. Calogero
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  3. Maria Konstandi
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  4. Themis C. Kamilaris
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  6. George P. Chrousos
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Correspondence to Elizabeth O. Johnson.

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Johnson, E.O., Calogero, A.E., Konstandi, M. et al. Effects of experimentally induced hyperthyroidism on central hypothalamic–pituitary–adrenal axis function in rats: in vitro and in situ studies. Pituitary 16, 275–286 (2013). https://doi.org/10.1007/s11102-012-0417-5

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