ECE2018 Guided Posters Thyroid non cancer (9 abstracts)
Identification of new thyroid hormone dependent biomarkers for a successful replacement therapy
Sebastian Nock 1 , Kornelia Johann 1 , Lisbeth Harder 1 , Carolin S Höfig 2 , Vanessa Kracke 3 , Beatrice Engelmann 3 , Georg Homuth 3 , Uwe Völker 3 , Jens Mittag 1 & Georg Brabant 1
1Department of Internal Medicine I - Molecular Endocrinology, University of Lübeck, Lübeck, Germany; 2Institute of Experimental Endocrinology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 3Department of Functional Genomics, Universitätsmedizin Greifswald, Greifswald, Germany.
Thyroid hormones (TH) play a pivotal role in embryonal and postnatal development in vertebrates, hence, their secretion is highly regulated. In clinical practice TSH and free T4 (fT4) are commonly used as the most reliable parameters to evaluate the TH status. But they only represent the TH receptor β driven status of the hypothalamic-pituitary-thyroid axis while organ or tissue specific TH availability may be different. This discrepancy originates in the tissue specific unequal distribution of proteins modulating local T3 signalling like TH transporters, deiodinases and TH receptors (TRα and TRβ). To identify patients with tissue specific hypo – or hyperthyroidism, new biomarkers are urgently needed. By comparing studies of experimental thyrotoxicosis in human and mouse using OMICs techniques, we discovered 16 serum proteins concordantly regulated in both species, which are predominantly expressed in liver, lymphoid system or extracellular matrix. To validate these putative targets, we conducted a follow-up mouse study with a Methimazol and sodium perchlorate induced hypothyroid group and a T3 or T4 induced hyperthyroid group. Subsequent qPCR analysis revealed gene expression changes of our candidates under hypo – and/or hyperthyroid conditions in liver, bone and spleen. To characterise these putative biomarkers in greater detail, we aimed to determine the secreting cell types and validate their T3-dependence in different model systems. We therefore investigated target gene expression of the human hepatocyte cell line HepG2, primary murine osteoclast, -blasts and isolated murine B-cells, T-cells and monocytes under either eu-, hypo- or hyperthyroid conditions or with a mutation in either TRα or TRβ or both. Among these candidates the expression of the macrophage derived protein, CD5L, was highly T3-dependent in liver, spleen and bone. CD5L is thus regarded as the most promising putative TH – biomarker to be further investigated under pathophysiological clinical conditions.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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