Endocrine Abstracts

Thyroid hormone transporters at the plasma membrane govern intracellular thyroid hormone concentrations. MCT8 represents a key thyroid hormone transporter. MCT8 deficiency (also known as Allan-Herndon-Dudley syndrome) is a devastating developmental disorder caused by mutations in the MCT8 gene (located on the X-chromosome), with an estimated prevalence of 1:70.000 males. The phenotype comprises (1) a &#...

Since thyroid hormone is a key regulator of metabolism, changes in thyroid hormone signaling have widespread effects. Thyroid state changes during aging and vice versa lifespan is affected by thyroid state. However, underlying mechanisms remain elusive. DNA damage importantly contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair.In different mouse models of premature (DNA-repair deficient animals)...

Introduction: Adequate thyroid hormone availability during early life is crucial for normal child growth and development. Fetal growth in utero heavily depends on angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor (VEGF) whereas soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of VEGF and PlGF signaling. Since the thyroid is a highly vascularized organ, we hypothesized t...

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...

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...

Background: Postpartum depression (PPD) is a common mental health disorder with a major impact on maternal health and wellbeing and offspring development. Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for postpartum thyroiditis and via this link, it is hypothesized that TPOAb positivity is a risk factor for PPD. However, the results of currently available single center studies are heterogeneous and affected by major study limitations.<p class="abstext"...

Background: Postpartum depression (PPD) is a common mental health disorder with a major impact on maternal health and wellbeing and offspring development. Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for postpartum thyroiditis and via this link, it is hypothesized that TPOAb positivity is a risk factor for PPD. However, the results of currently available single center studies are heterogeneous and affected by major study limitations.<p class="abstext"...

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...

Background: Patients with medullary thyroid carcinoma (MTC), a neuroendocrine tumour derived from the parafollicular C-cells, often present with metastasized disease. Survival strongly correlates with stage of disease at diagnosis, illustrating the need for early diagnosis. Calcitonin (CT), a well-established tumour marker for MTC, is limited by a high rate of false positives in the screening phase. Promising new markers for MTC are procalcitonin (PCT) and progastrin releasin...

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...