Skip to main content
Log in

Alterations of the daily rhythms of HPT axis induced by chronic unpredicted mild stress in rats

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The relationship between thyroid function and depression has long been recognized. Patients with thyroid disorders are more prone to develop depressive symptoms and conversely depression may be accompanied by various subtle thyroid abnormalities. However, the daily rhythm alteration of the functions of the hypothalamus pituitary thyroid axis (HPT) is uncertain. In the present study, we investigated the effects of chronic unpredictable mild stress (CUMS) on the daily rhythm alterations of triiodothyronine (T3), thyroxine (T4), and Thyroid Stimulating Hormone (TSH) in the plasma. We found that CUMS led to depressive-like behavior and the daily rhythm of T3, T4, and TSH in the plasma being disturbed, as well the plasma levels of T3 and T4 decreased compared to control group. Our findings indicate that CUMS not only induce hypofunction of HPT axis but also the disturbance of daily rhythm of PHT axis in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. O.M. Wolkowitz, A.J. Rothschild, Psychoneuroendocrinology: the scientific basis of clinical practice (American Psychiatric, Washington, 2003)

    Google Scholar 

  2. R. Cooper, B. Lerer, The use of thyroid hormones in the treatment of depression. Harefuah 149(8), 529–534 (2010)

    PubMed  Google Scholar 

  3. C.U. Pae, L. Mandelli, C. Han, B.J. Ham, P.S. Masand, A.A. Patkar, D.C. Steffens, D. De Ronchi, A. Serretti, Thyroid hormones affect recovery from depression during antidepressant treatment. Psychiatry Clin. Neurosci. 63(3), 305–313 (2009)

    Article  CAS  PubMed  Google Scholar 

  4. C.E. Fardella, R.A. Artigas, S. Gloger, M. Jimenez, C.A. Carvajal, P.M. Krall, D. Quiroz, C. Campino, L.M. Mosso, Refractory depression in a patient with peripheral resistance to thyroid hormone (RTH) and the effect of triiodothyronine treatment. Endocrine 31(3), 272–279 (2007)

    Article  CAS  PubMed  Google Scholar 

  5. B.S. McEwen, Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology 22(2), 108–124 (2000)

    Article  CAS  PubMed  Google Scholar 

  6. G.A. Cremaschi, G. Gorelik, A.J. Klecha, A.E. Lysionek, A.M. Genaro, Chronic stress influences the immune system through the thyroid axis. Life Sci. 67(26), 3171–3179 (2000)

    Article  CAS  PubMed  Google Scholar 

  7. D.M. Silberman, M. Wald, A.M. Genaro, Effects of chronic mild stress on lymphocyte proliferative response. Participation of serum thyroid hormones and corticosterone. Int. Immunopharmacol. 2(4), 487–497 (2002)

    Article  CAS  PubMed  Google Scholar 

  8. R.A. Lasser, R.J. Baldessarini, Thyroid hormones in depressive disorders: a reappraisal of clinical utility. Harv. Rev. Psychiatry 4(6), 291–305 (1997)

    Article  CAS  PubMed  Google Scholar 

  9. J.W. Mason, A review of psychoendocrine research on the pituitary–thyroid system. Psychosom. Med. 30(5), 666–681 (1968)

    Article  PubMed  Google Scholar 

  10. J. Mason, S. Southwick, R. Yehuda, S. Wang, S. Riney, D. Bremner, D. Johnson, H. Lubin, D. Blake, G. Zhou et al., Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder. Arch. Gen. Psychiatry 51(8), 629–641 (1994)

    Article  CAS  PubMed  Google Scholar 

  11. M. Bauer, S. Priebe, I. Kurten, K.J. Graf, A. Baumgartner, Psychological and endocrine abnormalities in refugees from East Germany: part I. Prolonged stress, psychopathology, and hypothalamic–pituitary–thyroid axis activity. Psychiatry Res. 51(1), 61–73 (1994)

    Article  CAS  PubMed  Google Scholar 

  12. Y. Turakulov, R.B. Burikhanov, P.P. Patkhitdinov, A.I. Myslitskaya, Influence of immobilization stress on the level of secretion of thyroid hormones. Neurosci. Behav. Physiol. 24(6), 462–464 (1994)

    Article  PubMed  Google Scholar 

  13. G. Cizza, L.S. Brady, M.E. Esclapes, M.R. Blackman, P.W. Gold, G.P. Chrousos, Age and gender influence basal and stress-modulated hypothalamic–pituitary–thyroidal function in Fischer 344/N rats. Neuroendocrinology 64(6), 440–448 (1996)

    Article  CAS  PubMed  Google Scholar 

  14. J. Josko, Liberation of thyreotropin, thyroxine and triiodothyronine in the controllable and uncontrollable stress and after administration of naloxone in rats. J. Physiol. Pharmacol. 47(2), 303–310 (1996)

    CAS  PubMed  Google Scholar 

  15. I. Pollard, J.R. Bassett, K.D. Cairncross, Plasma thyroid hormone and glucocorticosteroid concentrations in the male rat following prolonged exposure to stress. Aust. J. Biol. Sci. 32(2), 237–242 (1979)

    CAS  PubMed  Google Scholar 

  16. R.J. Servatius, B.H. Natelson, R. Moldow, L. Pogach, F.X. Brennan, J.E. Ottenweller, Persistent neuroendocrine changes in multiple hormonal axes after a single or repeated stressor exposures. Stress 3(4), 263–274 (2000)

    Article  CAS  PubMed  Google Scholar 

  17. N. Kioukia-Fougia, K. Antoniou, S. Bekris, C. Liapi, I. Christofidis, Z. Papadopoulou-Daifoti, The effects of stress exposure on the hypothalamic–pituitary–adrenal axis, thymus, thyroid hormones and glucose levels. Prog. Neuropsychopharmacol. Biol. Psychiatry 26(5), 823–830 (2002)

    Article  CAS  PubMed  Google Scholar 

  18. P. Langer, O. Foldes, R. Kvetnansky, J. Culman, T. Torda, F. El Daher, Pituitary–thyroid function during acute immobilization stress in rats. Exp. Clin. Endocrinol. 82(1), 51–60 (1983)

    Article  CAS  PubMed  Google Scholar 

  19. S.X. Li, L.J. Liu, W.G. Jiang, L. Lu, Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in rats. J Neurochem 109(6), 1668–1679 (2009)

  20. N. Kioukia, S. Bekris, K. Antoniou, Z. Papadopoulou-Daifoti, I. Christofidis, Effects of chronic mild stress (CMS) on thyroid hormone function in two rat strains. Psychoneuroendocrinology 25(3), 247–257 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. K. Kondo, M.S. Harbuz, A. Levy, S.L. Lightman, Inhibition of the hypothalamic–pituitary–thyroid axis in response to lipopolysaccharide is independent of changes in circulating corticosteroids. Neuroimmunomodulation 4(4), 188–194 (1997)

    CAS  PubMed  Google Scholar 

  22. O. Marti, A. Gavalda, T. Jolin, A. Armario, Effect of regularity of exposure to chronic immobilization stress on the circadian pattern of pituitary adrenal hormones, growth hormone, and thyroid stimulating hormone in the adult male rat. Psychoneuroendocrinology 18(1), 67–77 (1993)

    Article  CAS  PubMed  Google Scholar 

  23. P. Willner, Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134(4), 319–329 (1997)

    Article  CAS  PubMed  Google Scholar 

  24. W.G. Jiang, S.X. Li, S.J. Zhou, Y. Sun, J. Shi, L. Lu, Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus. Brain Res. 1399, 25–32 (2011)

    Article  CAS  PubMed  Google Scholar 

  25. M.B. Stein, T.W. Uhde, Triiodothyronine potentiation of tricyclic antidepressant treatment in patients with panic disorder. Biol. Psychiatry 28(12), 1061–1064 (1990)

    Article  CAS  PubMed  Google Scholar 

  26. N. Kioukia-Fougia, I. Christofidis, N. Strantzalis, Physicochemical conditions affecting the formation/stability of serum complexes and the determination of prostate-specific antigen (PSA). Anticancer Res. 19(4B), 3315–3320 (1999)

    CAS  PubMed  Google Scholar 

  27. D.L. Helmreich, D.B. Parfitt, X.Y. Lu, H. Akil, S.J. Watson, Relation between the hypothalamic–pituitary–thyroid (HPT) axis and the hypothalamic–pituitary–adrenal (HPA) axis during repeated stress. Neuroendocrinology 81(3), 183–192 (2005)

    Article  CAS  PubMed  Google Scholar 

  28. H. Hohtari, A. Pakarinen, A. Kauppila, Serum concentrations of thyrotropin, thyroxine, triiodothyronine and thyroxine binding globulin in female endurance runners and joggers. Acta. Endocrinol. (Copenh) 114(1), 41–46 (1987)

    CAS  Google Scholar 

  29. K. Opstad, Circadian rhythm of hormones is extinguished during prolonged physical stress, sleep and energy deficiency in young men. Eur. J. Endocrinol. 131(1), 56–66 (1994)

    Article  CAS  PubMed  Google Scholar 

  30. A. Baumgartner, K.J. Graf, I. Kurten, H. Meinhold, The hypothalamic–pituitary–thyroid axis in psychiatric patients and healthy subjects: Parts 1–4. Psychiatry Res. 24(3), 271–332 (1988)

    Article  CAS  PubMed  Google Scholar 

  31. L.R. Frick, M. Rapanelli, U.A. Bussmann, A.J. Klecha, M.L. Arcos, A.M. Genaro, G.A. Cremaschi, Involvement of thyroid hormones in the alterations of T-cell immunity and tumor progression induced by chronic stress. Biol. Psychiatry 65(11), 935–942 (2009)

    Article  CAS  PubMed  Google Scholar 

  32. E.L. Olivares, C. Silva-Almeida, F.M. Pestana, R. Sonoda-Cortes, I.G. Araujo, N.C. Rodrigues, A.S. Mecawi, W.S. Cortes, M.P. Marassi, L.C. Reis, F.F. Rocha, Social stress-induced hypothyroidism is attenuated by antidepressant treatment in rats. Neuropharmacology 62(1), 446–456 (2012)

    Article  CAS  PubMed  Google Scholar 

  33. P. Monteleone, Circadian rhythm disturbances in depression: implications for treatment and quality of remission. Medicographia 31(2), 132–139 (2009)

    Google Scholar 

  34. S.X. Li, L.J. Liu, L.Z. Xu, L. Gao, X.F. Wang, J.T. Zhang, L. Lu, Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment. Psychoneuroendocrinology 38(11), 2789–2799 (2013)

    Article  CAS  PubMed  Google Scholar 

  35. E. Souetre, E. Salvati, T.A. Wehr, D.A. Sack, B. Krebs, G. Darcourt, Twenty-four-hour profiles of body temperature and plasma TSH in bipolar patients during depression and during remission and in normal control subjects. Am. J. Psychiatry 145(9), 1133–1137 (1988)

    Article  CAS  PubMed  Google Scholar 

  36. C.B. Nemeroff, D.L. Evans, Thyrotropin-releasing hormone (TRH), the thyroid axis, and affective disorder. Ann. N. Y. Acad. Sci. 553, 304–310 (1989)

    Article  CAS  PubMed  Google Scholar 

  37. P.T. Loosen, A.J. Prange Jr, Serum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: a review. Am. J. Psychiatry 139(4), 405–416 (1982)

    Article  CAS  PubMed  Google Scholar 

  38. C. Kirkegaard, The thyrotropin response to thyrotropin-releasing hormone in endogenous depression. Psychoneuroendocrinology 6(3), 189–212 (1981)

    Article  CAS  PubMed  Google Scholar 

  39. A.J. Kastin, R.H. Ehrensing, D.S. Schalch, M.S. Anderson, Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone. Lancet 2(7780), 740–742 (1972)

    Article  CAS  PubMed  Google Scholar 

  40. A.J. Prange, P.P. Lara, I.C. Wilson, L.B. Alltop, G.R. Breese, Effects of thyrotropin-releasing hormone in depression. Lancet 2(7785), 999–1002 (1972)

    Article  PubMed  Google Scholar 

  41. M.P. Hage, S.T. Azar, The link between thyroid function and depression. J. Thyroid Res. 2012(2012), 1–8 (2012)

    Article  Google Scholar 

  42. F. Duval, M.C. Mokrani, F.G. Lopera, T.S. Diep, H. Rabia, S. Fattah, Thyroid axis activity and suicidal behavior in depressed patients. Psychoneuroendocrinology 35(7), 1045–1054 (2010)

    Article  CAS  PubMed  Google Scholar 

  43. J. Jokinen, M. Samuelsson, A.L. Nordstrom, P. Nordstrom, HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters. J. Affect. Disord. 111(1), 119–124 (2008)

    Article  CAS  PubMed  Google Scholar 

  44. W. Foltyn, E. Nowakowska-Zajdel, A. Danikiewicz, A. Brodziak, Hypothalamic–pituitary–thyroid axis in depression. Psychiatria Pol. 36(2), 281–292 (2002)

    Google Scholar 

  45. C. Peteranderl, I.A. Antonijevic, A. Steiger, H. Murck, K. Held, R.M. Frieboes, M. Uhr, L. Schaaf, Nocturnal secretion of TSH and ACTH in male patients with depression and healthy controls. J. Psychiatr. Res. 36(3), 189–196 (2002)

    Article  PubMed  Google Scholar 

  46. D.F. Zhu, Z.X. Wang, D.R. Zhang, Z.L. Pan, S. He, X.P. Hu, X.C. Chen, J.N. Zhou, fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism. Brain 129(Pt 11), 2923–2930 (2006)

    Article  PubMed  Google Scholar 

  47. E. Taskin, A.S. Artis, S. Bitiktas, N. Dolu, N. Liman, C. Suer, Experimentally induced hyperthyroidism disrupts hippocampal long-term potentiation in adult rats. Neuroendocrinology 94(3), 218–227 (2011)

    Article  CAS  PubMed  Google Scholar 

  48. M.H. Samuels, K.G. Schuff, N.E. Carlson, P. Carello, J.S. Janowsky, Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 92(7), 2545–2551 (2007)

    Article  CAS  PubMed  Google Scholar 

  49. J.M. Guimaraes, C. de Souza Lopes, J. Baima, R. Sichieri, Depression symptoms and hypothyroidism in a population-based study of middle-aged Brazilian women. J. Affect. Disord. 117(1–2), 120–123 (2009)

    Article  PubMed  Google Scholar 

  50. M.S. Gold, A.L. Pottash, I. Extein, Hypothyroidism and depression. Evidence from complete thyroid function evaluation. JAMA 245(19), 1919–1922 (1981)

    Article  CAS  PubMed  Google Scholar 

  51. C.E. Fardella, R.A. Artigas, S. Gloger, M. Jimenez, C.A. Carvajal, P.M. Krall, D. Quiroz, C. Campino, L.M. Mosso, Refractory depression in a patient with peripheral resistance to thyroid hormone (RTH) and the effect of triiodothyronine treatment. Endocrine 31(3), 272–278 (2007)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the Natural Science Foundation of China (Nos. 81171251, 31230033, and 91132716) and Humanity and Social Science of Ministry of Education of China (No. 12YJCZH063).

Conflict of interest

The authors declare that they do not have any conflicts of interest related to the data presented in this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Su-Xia Li.

Additional information

Tian-You Guo and Li-Jing Liu have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, TY., Liu, LJ., Xu, LZ. et al. Alterations of the daily rhythms of HPT axis induced by chronic unpredicted mild stress in rats. Endocrine 48, 637–643 (2015). https://doi.org/10.1007/s12020-014-0314-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-014-0314-y

Keywords

Navigation