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Cited by 110Thyroid Disorders and TreatmentsSepsis Diagnosis and TreatmentAdrenal Hormones and Disorders

Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock

Rodriguez‐Perez, Alfonso, Palos‐Paz, Fernando, Kaptein, Ellen, Visser, Theo J., Dominguez‐Gerpe, L., Alvarez‐Escudero, Julian, Lado‐Abeal, Joaquin·2008·Clinical Endocrinology
DOI 10.1111/j.1365-2265.2007.03102.x
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Abstract

Summary: Objective Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Design Hospitalized patients were divided into a control and a septic shock NTIS group. Measurement Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements. Results The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls. Conclusions In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.

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Crossref · 10.1111/j.1365-2265.2007.03102.x

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  • Muscle UCP3 and myogenin mRNA expression, which are both T3 target genes, are unaltered in septic patients compared to controls.

    “However, muscle UCP3 and myogenin mRNA expression, which are both T3 target genes, are unaltered in septic patients compared to controls [29].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [29]

  • Muscle DIO2 is differentially affected during illness: acute inflammation in mice increases muscle Dio2 mRNA expression, while bacterial sepsis decreases Dio2 mRNA expression both in mice and humans.

    “Muscle DIO2 is differentially affected during illness. Acute inflammation in mice increases muscle Dio2 mRNA expression, while bacterial sepsis decreases Dio2 mRNA expression both in mice [28] and humans [29].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [29]

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Authors
Rodriguez‐Perez, A., Palos‐Paz, F., Kaptein, E., Visser, T. J., Dominguez‐Gerpe, L., Alvarez‐Escudero, J., & Lado‐Abeal, J.
Affiliations
  • Universidade de Santiago de Compostela (ES)
  • Erasmus MC (NL)
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2007-10-08
Volume
68
Issue
5
Pages
821-827
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/j.1365-2265.2007.03102.x
OpenAlex
W1988529706
Cited by
110
References
42
Citations by year
2025: 4 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 11 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 2 · 2013: 8 · 2012: 3
FWCI
4.64
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
low T3 syndrome, septic shock, thyroid hormone receptor, thyroid hormone deiodinases, skeletal muscle, subcutaneous adipose tissue, retinoid X receptor, thyroid hormone action, reverse T3, UCP3, MCT8, gene expression, energy metabolism
MeSH terms
Adipose Tissue, Adult, Aged, Aged, 80 and over, Female, Humans, Iodide Peroxidase, Male, Middle Aged, Shock, Septic, Thyroid Diseases, Gene Expression Regulation, Enzymologic, Case-Control Studies, Muscle, Skeletal

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