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Effects of short- and long-duration hypothyroidism on function of the rat hypothalamic-pituitary-adrenal axis

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Abstract

The effects of hypothyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis were investigated in adult male rats. HPA axis function was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats or in thyroidectomized rats for 7 (short-term hypothyroidism) or 60 (long-term hypothyroidism) days. Peripheral ACTH and corticosterone responses to insulin-induced hypoglycemia and interleukin (IL)-1α stimulation were used to indirectly assess the hypothalamic CRH neuron. Hypothyroidism resulted in exaggerated ACTH responses to both hypoglycemic stress and IL-1α administration. The adrenal cortex of hypothyroid animals showed a significant reduction in adrenal reserves, as assessed by its response to low-dose ACTH, following suppression of the HPA axis with dexamethasone. Hypothyroid rats were also associated with significant decreases in cerebrospinal fluid corticosterone concentrations and decreased adrenal weights. The findings suggest that experimentally induced hypothyroidism is associated with a mild, yet significant, adrenal insufficiency, which involves abnormalities in all components of the HPA axis.

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References

  1. Ingbar SH. Management of emergencies. IX. Thyroid storm. N Engl J Med 1996, 274: 1252–4.

    Article  Google Scholar 

  2. Barsano CP. Hypothyroidism. In: Conn’s Current Therapy, Philadelphia: WB Saunders Co. 1991, 596–600.

    Google Scholar 

  3. Stiefelhagen P. Hypothyroidism and adrenal cortex insufficiency. Hormone replacement—individually controlled. MMW Fortschr Med 2010, 152: 14–6.

    Google Scholar 

  4. Tohei A. Studies on the functional relationship between thyroid, adrenal and gonadal hormones. J Reprod Dev 2004, 50: 9–20.

    Article  PubMed  Google Scholar 

  5. Kamilaris TC, DeBold CR, Johnson EO, et al. Effects of short and long duration hypothyroidism and hyperthyroidism on the plasma adrenocorticotropin and corticosterone responses to ovine corticotropin-releasing hormone in rats. Endocrinology 1991, 128: 2567–76.

    Article  PubMed  Google Scholar 

  6. Murakami N, Hayafuji C, Takahashi K. Thyroid hormone maintains normal circadian rhythm of blood corticosterone levels in the rat by restoring the release and synthesis of ACTH after thyroidectomy. Acta Endocrinol (Copenh) 1984, 107: 519–24.

    Google Scholar 

  7. Shi ZX, Levy A, Lightman SL. Thyroid hormone-mediated regulation of corticotropin releasing hormone messenger ribonucleic acid in the rat. Endocrinology 1994, 134: 1577–80.

    PubMed  Google Scholar 

  8. Tohei A, Akai M, Tomabechi T, Mamada M, Taya K. Adrenal and gonadal function in hypothyroid adult make rats J Endocrinol 1997, 152: 147–54.

    Article  PubMed  Google Scholar 

  9. Kamilaris TC, DeBold CR, Pavlou SN, Island DP, Hoursanidis A, Orth DN. Effect of altered thyroid hormone levels on hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab 1987, 65: 994–9.

    Article  PubMed  Google Scholar 

  10. Donald RA, Espiner EA. The plasma cortisol and corticotrope response to hypoglycemia following adrenal steroid and ACTH administration. J Clin Endocrinol Metab 1975, 41: 1–6.

    Article  PubMed  Google Scholar 

  11. Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W. Interleukin-1 stimulates the secretion of hypothalamiccorticotropin-releasing factor. Science 1987, 238: 522–4.

    Article  PubMed  Google Scholar 

  12. Calogero AE, Kamilaris TC, Bernardini R, Johnson EO, Chrousos GP, Gold PW. Effects of peripheral benzodiazepine receptor ligands on hypothalamic-pituitary-adrenal axis function in the rat. J Pharmacol Exp Ther 1990, 253: 729–37.

    PubMed  Google Scholar 

  13. Tohei A, Watanabe G, Taya K. Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion. J Endocrinol 1998, 156: 395–400.

    Article  PubMed  Google Scholar 

  14. Dallman MF, Akana SF, Cascio CS, Darlington DN, Jacobson L, Levin N. Regulation of ACTH secretion: variations on a theme of B. Recent Prog Horm Res 1987, 43: 113–67.

    PubMed  Google Scholar 

  15. Gordon GG, Southren AL. Thyroid — hormone effects on steroid — hormone metabolism. Bull N Y Acad Med 1977, 53: 241–59.

    PubMed Central  PubMed  Google Scholar 

  16. Peterson RE. The influence of the thyroid on adrenal cortical function. J Clin Invest 1958, 37: 736–43.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Vierhapper H, Nowotny P, Waldhäusl W. Increase in serum concentrations of thyroxine-binding globulin and of cortisol-binding globulin after the induction of normal thyroid function in previously hyperthyroid patients. Thyroid 1999, 9: 1085–7.

    Article  PubMed  Google Scholar 

  18. Dumoulin SC, Perret BP, Bennet AP, Caron PJ. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans. Eur J Endocrinol 1995, 132: 594–8.

    Article  PubMed  Google Scholar 

  19. Dakine N, Oliver C, Grino M. Effects of experimental hypothyroidism on the development of the hypothalamo-pituitary-adrenal axis in the rat. Life Sci 2000, 67: 2827–44.

    Article  PubMed  Google Scholar 

  20. Mountjoy KG, Wong J. Obesity, diabetes and functions for proopiomelanocortin-derived peptides. Mol Cell Endocrinol 1997, 128: 171–7.

    Article  PubMed  Google Scholar 

  21. Besedovsky HO, del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 1996, 17: 64–102.

    Article  PubMed  Google Scholar 

  22. Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitaryadrenal axis by cytokines: actions and mechanisms of action, Physiol Rev 1999, 79: 1–71.

    PubMed  Google Scholar 

  23. Hauger RL, Aguilera G. Regulation of corticotropin-releasing hormone receptors and hypothalamic pituitary adrenal axis responsiveness during cold stress. J Neuroendocrinol 1992, 4: 617–24.

    Article  PubMed  Google Scholar 

  24. Jackson IM, Hassan TH, Prentice CR, Browning MC. Insulin-induced hypoglycemia as a test of pituitary-adrenal function in thyrotoxicosis. J Clin Endocrinol Metab 1966, 26: 545–9.

    Article  PubMed  Google Scholar 

  25. Lizcano F, Rodríguez JS. Thyroid hormone therapy modulates hypothalamo-pituitary-adrenal axis. Endocrine J 2011, 58: 137–42.

    Article  Google Scholar 

  26. Chang SC, Thibodeaux JR, Eastvold ML, et al. Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS). Toxicology 2008, 243: 330–9.

    Article  PubMed  Google Scholar 

  27. van Raaij JA, Frijters CM, van den Berg KJ. Hexachlorobenzeneinduced hypothyroidism. Involvement of different mechanisms by parent compound and metabolite. Biochem Pharmacol 1993, 46: 1385–91.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

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

    E. O. Johnson MD

  2. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Catania, Italy

    E. O. Johnson MD, T. C. Kamilaris, A. E. Calogero & G. P. Chrousos

  3. Section of Endocrinology, Andrology and Internal Medicine, Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy

    A. E. Calogero

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

    M. Konstandi

  5. 1st Department of Pediatrics, University of Athens, School of Medicine, Athens, Greece

    G. P. Chrousos

Authors
  1. E. O. Johnson MD
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  2. T. C. Kamilaris
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  3. A. E. Calogero
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  4. M. Konstandi
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  5. G. P. Chrousos
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Correspondence to E. O. Johnson MD.

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Johnson, E.O., Kamilaris, T.C., Calogero, A.E. et al. Effects of short- and long-duration hypothyroidism on function of the rat hypothalamic-pituitary-adrenal axis. J Endocrinol Invest 36, 104–110 (2013). https://doi.org/10.3275/8454

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  • DOI: https://doi.org/10.3275/8454

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