Searchable abstracts of presentations at key conferences in endocrinology

ea0084ps1-04-34 | Thyroid Hormone Transporters and Development | ETA2022

The dawning of deiodinases: an outer ring deiodinase activity in the social amoeba dictyostelium discoideum with high affinity for reverse t3

Meima Marcel , Schaap Pauline , Edward Visser W.

Background: Conservation of genes involved in TH transport, metabolism and action can reveal clues about the origins of TH signaling. A deiodinase homologue (DdDio) was previously identified in the social amoeba Dictyostelium discoideum (Singh, 2014). Dictyostelium cells live as single cell amoebae in soil where they feed on bacteria. However, upon starvation a developmental program is initiated that results in the formation of a multicellular fruiti...

ea0084ps1-04-31 | Thyroid Hormone Transporters and Development | ETA2022

The role of type 3 deiodinase in a human model for early brain development

Lopez Marti Anna , Gunhanlar Nilhan , Meima Marcel , Edward Visser W.

Background: Disrupted thyroid hormone (TH) homeostasis has devastating effects on human neurodevelopment. THs are critical signaling molecules in neurodevelopment, acting on differentiation of neural cells, migration, synaptogenesis and myelination, with deiodinases governing intracellular TH concentrations in a spatiotemporal manner. It is remarkable that fetal neural cells, while being key target cells of TH, exhibit strong activity of the TH inactivating enzyme DIO3. Curren...

ea0084ps1-04-36 | Thyroid Hormone Transporters and Development | ETA2022

Thyroid hormone signaling in a human cellular model for early brain development

Gunhanlar Nilhan , Tellez Garcia Juan , Lopez Marti Anna , Shokrollahi Faezeh , Meima Marcel , Edward Visser W.

Background and Objective: Disrupted thyroid hormone (TH) signaling has devastating effects on human neurodevelopment. The molecular mechanisms underlying TH regulation and action are largely based on animal models. However, animal models are limited in revealing some of the most fundamental aspects of neurodevelopment that are unique to humans. We employed human induced pluripotent stem cell (iPSC) technology to study the effects of T3 on neurodevelopmental processes in a huma...

ea0092ps2-20-09 | Thyroid hormone receptors basic | ETA2023

The relevance of histidine 175 in thyroid hormone receptor alpha 1 for co-repressor binding revealed by a family carrying a H175R variant

Liao Wenjun , Meima Marcel , Groeneweg Stefan , Hannema Sabine , Edward Visser W.

Background: Resistance to thyroid hormone (TH) alpha (RTHα), caused by heterozygous mutations in THRA, is characterized by abnormal thyroid function tests and features due to tissue-specific hypothyroidism, including disproportional short stature, variable motor and cognitive defects, macrocephaly and macroglossia, constipation and anemia. Mutant receptors display defective T3 binding resulting in impaired transcriptional activity. Dominant negative inhibition of the WT r...

ea0092ps3-30-01 | Thyroid Physiology in Periphery & Development Basic | ETA2023

Developing an animal-free testing battery for thyroid hormone related developmental neurotoxicity

Dierichs Nathalie , Meima Marcel , Edward Visser W. , Piersma Aldert , Hessel Ellen , Peeters Robin

Background: Over the last few decades, in vivo animal experiments have been the gold standard for the assessment of safety of chemicals and pharmaceuticals for human health. However, in vivo animal data has limited relevance for toxicity prediction in humans, especially considering species-specific issues of age, sex and exposure in different life-stages. Within the Virtual Human Platform for Safety Assessment (VHP4Safety) project we aim to develop an animal-...

ea0084ps2-09-84 | Thyroid Hormone ACTION | ETA2022

Molecular mechanisms underlying action of triac in resistance to thyroid hormone BETA (RTHβ)

Liao Wenjun , van Geest Ferdy , Marelli Federica , Campi Irene , Moran Carla , Lyons Greta , Agostini Maura , Peeters Robin , Chatterjee Krishna , Persani Luca , Meima Marcel , Edward Visser W.

Background: Resistance to thyroid hormone (TH) beta (RTHβ), caused by mutations in THRB, is characterized by elevated serum (F)T4 accompanied by non-suppressed TSH concentrations. Disease features arise from variable resistance to TH action in tissues expressing Thyroid Hormone Receptor (TR) β (hypothalamus, pituitary, liver) and from thyrotoxic effects in tissues expressing TRα (heart, bone, brain). In symptomatic patients, treatment mainly involves be...

ea0092op-01-06 | Oral Session 1: Highlights in Thyroidology: in Memory of Jacques Dumont | ETA2023

Phenotypic differences in resistance to thyroid hormone alpha: differential recruitment of cofactors by thyroid hormone receptor alpha 1 mutants

Meima Marcel , Wejaphikul Karn , Liao Wenjun , Leeuwenburgh Selmar , Zeneyedpour Lona , Dekker Lennard , van Ijcken Wilfred F. , Luider Theo M. , Peeters Robin , Edward Visser W.

Background: Resistance to thyroid hormone alpha (RTHα), caused by mutations in the T3-receptor alpha 1 (TRα1) isoform, includes growth retardation, intellectual disability, and abnormal thyroid function tests. The current paradigm entails that disease features arise from decreased T3 action in TRα1-expressing tissues. However, also for patients that carry mutations that completely abolish T3-stimulated activity, neurological features vary strongly, ranging from ...

ea0084op-08-40 | Oral Session 8: Basic 2 | ETA2022

Disrupted trans-placental thyroid hormone transport in a human model for MCT8 deficiency

Chen Zhongli , Leeuwenburgh Selmar , Zijderveld Wouter , Broekhuizen Broekhuizen M. , Tan Lunbo , Neuman Neuman R.I. , Jongejan Rutchanna , de Rijke Yolanda , K. Reiss Irwin , H. J. Danser Danser A. , Peeters Robin , Meima Marcel , Edward Visser W.

Objectives: During prenatal neurodevelopment, maternal-to-fetal thyroxine (T4) transfer is critical, particularly during the first half of pregnancy when the fetal thyroid gland is immature. Transcellular transport of thyroid hormones (TH) is facilitated by TH transporters. Monocarboxylate transporter 8 (MCT8) is a specific TH transporter that is crucial for transport of TH with a prominent expression at the blood-brain barrier. MCT8 deficiency is a rare disorder consisting of...

ea0084op-11-58 | Oral Session 11: Young Investigators / Basic | ETA2022

Integrated genomic, phenomic, functional and structural mapping of variants in thyroid hormone transporter MCT8

Groeneweg Stefan , Van Geest Ferdy , martin mariano , Dias Mafalda , Frazer Jonathan , Sterenborg Rosalie , de rooij linda , dolcetta-capuzzo anna , teumer alexander , Meima Marcel , Medici Marco , pablo nicola juan , marks debora , Edward Visser W.

Background: MCT8 deficiency is caused by loss-of-function (LoF) mutations in thyroid hormone (TH) transporter MCT8. Patients have developmental delay and abnormal thyroid function tests (TFTs). The large phenotypic variability is not understood. Moreover, phenotypes arising from LoF mutations could be employed to enhance understanding of physiology in the general population. Also, computational disease variant classifiers have poor predictive power to ascertain impact of MCT8 ...