Endocrine Abstracts

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.Methods: Heterozygous females were mat...

Thyroid hormones (THs) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8 and MCT10) are effective plasma membrane TH transporters expressed in the human placenta from 6 weeks of gestation. Both have been localized to human villous trophoblasts and extravillous trophoblasts (EVTs).Aims: Using HTR-8/SVneo cells as a model of 1st trimester EVTs, we assessed 1) T3 effects on gene expression, cell prolif...

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most differentiated thyroid tumours exhibit reduced iodide uptake, however, and the mechanisms accounting for this remain poorly understood. Pituitary tumor transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We recently reported that PTTG and its binding factor PBF, also a potent transfo...

Thyroid hormones (TH) are important for the development of the fetus and placenta. We have previously reported increased placental expression of the potent TH transporter, MCT8, with advancing gestation. The amino acid plasma membrane transporters, MCT10, LAT1, LAT2, and the organic anion transporters, OATP1A2 and OATP4A1, are also known to transport TH.Objective: To describe the ontogeny of these TH transporters and the obligate heterodimer of the LATs,...

Thyroid hormones play vital roles in fetal brain development. Mutations in MCT8, recently recognised as a specific thyroid hormone transporter, define a novel syndrome of severe X-linked psychomotor retardation and thyroid hormone resistance.N-TERA-2 (NT2) cells (human embryonal cells with characteristics of CNS precursors) were transiently transfected with either WT MCT8 or its L471P, R271H or S448X mutations, described in males affected by severe psych...

Introduction: New therapeutic strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. We recently utilised high throughput screening and identified FDA-approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. Categorisation revealed a high proportion of drugs that modulate proteostasis, with 6 of the top 15 targeting activity of...

The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is upregulated in multiple tumours including thyroid cancer. PBF overexpression mediates tumorigenic processes such as cell motility and accelerates thyroid cancer cell invasion. We have recently shown that both PBF phosphorylation at tyrosine 174 (Y174) and PBF endocytosis are required for PBF-stimulated thyroid and breast cancer cell migration and invasion. This prompted further investigation into a ph...

The most common form of endocrine cancer is differentiated thyroid cancer (DTC). Outcomes of DTC largely depend on radioiodine treatment, which is mediated the sodium-iodide symporter (NIS). However, many tumours exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transform...

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...