title: 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.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Clementine J J
authors.initials: CJ
authors.lastname: van Zeijl
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Surovtseva
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Joan
authors.initials: J
authors.lastname: Kwakkel
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Hermina C
authors.initials: HC
authors.lastname: van Beeren
authors.forename: J H Duncan
authors.initials: JH
authors.lastname: Bassett
authors.affiliation: Molecular Endocrinology Group, Department of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom.
authors.forename: J H
authors.initials: JH
authors.lastname: Duncan Bassett
authors.affiliation: Molecular Endocrinology Group, Department of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Williams
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and a.boelen@amc.uva.nl.
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
mesh_terms: D041721:3T3-L1 Cells; D002001:Adipose Tissue, Brown / Q000473:pathology; D052436:Adipose Tissue, White / Q000473:pathology; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002606:Charcoal / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007453:Iodide Peroxidase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology; D036361:Peptide Hormones / Q000235:genetics / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: C559612:GPB5 protein, mouse; D006023:Glycoproteins; D008070:Lipopolysaccharides; D036361:Peptide Hormones; D013963:Thyroid Hormones; C458339:thyrostimulin; D002606:Charcoal; D000242:Cyclic AMP; D007453:Iodide Peroxidase
keywords: inflammation; thyroid hormone; thyrostimulin; type II deiodinase