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Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2016 BioFactors, 43(3):415-423, 2017.

Summary Background Congenital hypothyroidism (CH) is a common endocrine disease that occurs in about 1:3000 newborns. In 80–85% of the cases, CH is presumably secondary to thyroid dysgenesis (TD), a defect in the organogenesis of the gland leading to an ectopic (30–45%), absent (agenesis, 35–40%) or hypoplastic (5%) thyroid gland. The pathogenesis of TD is still largely unknown. Most cases of TD are sporadic, although familial occurrences have occasionally been described. Recently, mutations in the PAX8 transcription factor have been identified in patients with TD. Objective Our aim was to identify and functionally characterize novel PAX8 mutations with autosomal dominant transmission responsible for TD. Design The PAX8 gene was sequenced in a mother and child both suffering from congenital hypothyroidism (CH) because of thyroid hypoplasia. Subsequently, expression vectors encoding the mutated PAX8 were generated, and the effects of the mutation on both the DNA-binding capability and the transcriptional activity were evaluated. Results PAX8 gene sequencing revealed a heterozygous mutation that consists of the substitution of a histidine residue with a glutamine at position 55 of the PAX8 protein (H55Q). When tested in cotransfection experiments with a thyroglobulin promoter reporter construct, the mutant protein turned out to be still able to bind DNA in Electrophoretic Mobility Shift Assay assays but transcriptionally inactive. Conclusions Our findings confirm the important role of PAX8 in normal thyroid development and support the evidence that in humans haploinsufficiency of PAX8 is associated with TD.

Benign hereditary chorea is an autosomal dominant disorder characterized by early onset nonprogressive chorea, caused by mutations of the thyroid transcription factor-1 (TITF-1) gene. Clinical heterogeneity has been reported and thyroid and respiratory abnormalities may be present. We describe 3 patients of an Italian family carrying the S145X mutation in the TITF-1 gene with mild motor delay, childhood onset dyskinesias, and subtle cognitive impairment. A child in the third generation presented with congenital hypothyroidism and neonatal respiratory distress. Imaging studies in 2 patients showed mild ventricular enlargement and empty sella at magnetic resonance imaging and hypometabolism of basal ganglia and cortex at 18-Fluoro-2-deoxy-glucose positron emission tomography. © 2010 Movement Disorder Society