ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P10 | DOI: 10.1530/endoabs.65.P10

Thyroid hormone receptors in the mouse kidney in health and chronic kidney disease

Elena Tasinato1, Kristien Boelaert2, David Long3 & Elisavet Vasilopoulou1

1Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham, UK; 2Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 3Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK

Introduction: Chronic kidney disease (CKD) is a devastating condition characterised by progressive loss of renal function that leads to end-stage renal disease. In patients with CKD there is increased prevalence of subclinical hypothyroidism. The importance of thyroid hormone (TH) action on kidney development, growth and physiology has been established, however the role of TH on kidney disease progression is not well understood.

Aim: To assess the expression of TH receptors in the healthy and diseased mouse kidney.

Methods: Immunofluorescent staining for TH receptors, TRα and TRβ, alongside renal cell markers (Lotus Tetragonolobus Lectin, proximal tubule; E-Cadherin, distal tubule; Dolichos Biflorus Agglutinin, collecting duct; Cd31, endothelial cells; F4/80, macrophages) was performed on healthy mouse kidneys and kidneys from mice with nephrotoxic serum nephritis, which mimics CKD. TH receptor TRα1 (Thra1), TRα2 (Thra2) and TRβ1 (Thrb1) mRNA levels in healthy and early (day 7) and late (day 21) stage nephrotoxic nephritis mouse kidney tissue homogenates were assessed by qPCR and circulating tri-iodothyronine was quantified by ELISA.

Results: TH receptors, TRα and TRβ, were localised to the renal medulla of the mouse kidney, namely on the apical side of distal tubules and collecting ducts. The localisation of the receptors was not affected by the disease state, but their abundance was significantly affected with increased Thra1 (P<0.001) and decreased Thra2 (P<0.05) mRNA levels in late stage nephrotoxic nephritis kidneys compared with controls. The concentration of circulating tri-iodothyronine was decreased (P<0.05) in mice with late stage nephrotoxic nephritis compared with controls.

Conclusion: The variation in TH receptor expression in health and disease suggests that kidney disease may influence the ability of renal distal tubule and collecting duct cells to respond to THs. Further work is needed to determine how this may influence kidney function.

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