Metallothionein induction by restraint stress: Role of glucocorticoids and IL-6

Joaquín Hernández, Javier Carrasco, Eva Belloso, Mercedes Giralt, Horst Bluethmann, Dae Kee Lee, Glen K. Andrews, Juan Hidalgo

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53 Scopus citations


Restraint stress increased liver metallothionein-I (MT-I) mRNA and MT-I + II protein levels. The glucocorticoid receptor antagonist RU 486 decreased this response. In contrast, adrenalectomy only decreased MT-I + I protein levels. Moreover, corticosterone or progesterone did not reverse the effect of RU 486. These results suggest that glucocorticoids are important for MT-I + II protein synthesis but not for MT-I mRNA accumulation during restraint stress, and that other factors must be involved in this process. Interleukin-6 (IL-6) deficient mice showed a significant decrease of restraint stress-induced liver MT-I mRNA levels (~ 30% of IL-6+/+ mice) up to ~ 4-5 hours after the onset of stress. Western blotting of hepatic nuclear proteins showed that the IL-6 responsive transcription factor Stat3, which has been shown to mediate MT induction by inflammation, was also activated by restraint stress. Results after extended periods of restraint stress indicate that IL-6 participates early and transiently in the process. The analysis of the expression of the acute phase plasma protein serum amyloid A suggests that restraint stress elicits an acute phase response similar to that caused by inflammation. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)791-796
Number of pages6
Issue number6
StatePublished - Jun 2000

Bibliographical note

Funding Information:
This study was supported, in part, by the CICYT SAF96-0189, CIRIT 1995SGR 00499 and the PSPGC PM98-0170 also supported, in part, by an NIH grant (ES05704) to GKA. J. Carrasco is supported by a fellowship of the CIRIT, FI/96-2613. The help of the Laboratori d’Anàlisi Bioquímica of the Departament de Bioquímica i Biologia Molecular is appreciated. The help of J. Cantófrom the Servei d’Estabulari is gratefully appreciated.


  • Acute phase response
  • Glucocorticoids
  • Interlukin 6
  • Metallothionein
  • Stress


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