Thyrostimulin deficiency does not alter peripheral responses to acute inflammation-induced nonthyroidal illness.

Abstract

Thyrostimulin, a putative glycoprotein hormone, comprises the subunits GPA2 and GPB5 and activates the TSH receptor (TSHR). The observation that proinflammatory cytokines stimulate GPB5 transcription suggested a role for thyrostimulin in the pathogenesis of nonthyroidal illness syndrome (NTIS). In the present study, we induced acute inflammation by LPS administration to GPB5(-/-) and WT mice to evaluate the role of thyrostimulin in peripheral thyroid hormone metabolism during NTIS. In addition to serum thyroid hormone concentrations, we studied mRNA expression and activity of deiodinase types I, II, and III (D1, D2, and D3) in peripheral T3 target tissues, including liver, muscle, and white and brown adipose tissue (WAT and BAT), of which the latter three express the TSHR. LPS decreased serum free (f)T4 and fT3 indexes to a similar extent in GPB5(-/-) and WT mice. Serum reverse (r)T3 did not change following LPS administration. LPS also induced significant alterations in tissue D1, D2, and D3 mRNA and activity levels, but only the LPS-induced increase in WAT D2 mRNA expression differed between GPB5(-/-) and WT mice. In conclusion, lacking GPB5 during acute illness does not affect the LPS-induced decrease of serum thyroid hormones while resulting in subtle changes in tissue D2 expression that are unlikely to be mediated via the TSHR.

• Authors: Clementine J J van Zeijl, Olga V Surovtseva, Joan Kwakkel, Hermina C van Beeren, J H Duncan Bassett, J H Duncan Bassett, Graham R Williams, Wilmar M Wiersinga, Eric Fliers, Anita Boelen
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 307 Issue 6 Pg. E527-37 (Sep 15 2014) ISSN: 1522-1555 [Electronic] United States
• PMID: 25117405 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• GPB5 protein, mouse
• Glycoproteins
• Lipopolysaccharides
• Peptide Hormones
• Thyroid Hormones
• thyrostimulin
• Charcoal
• Cyclic AMP
• Iodide Peroxidase

Topics

• 3T3-L1 Cells
• Adipose Tissue, Brown (pathology)
• Adipose Tissue, White (pathology)
• Animals
• CHO Cells
• Cell Line
• Charcoal (chemistry)
• Cricetinae
• Cricetulus
• Cyclic AMP (metabolism)
• Glycoproteins (deficiency, genetics, physiology)
• Humans
• Inflammation (chemically induced, metabolism, pathology)
• Iodide Peroxidase (metabolism)
• Lipopolysaccharides (pharmacology)
• Liver (pathology)
• Mice
• Mice, Knockout
• Muscle, Skeletal (pathology)
• Peptide Hormones (genetics, physiology)
• Thyroid Hormones (metabolism)