Endocrine Abstracts

Subtle irregularity in maternal thyroid status during the 1st trimester of pregnancy is associated with abnormalities of neurodevelopment in childhood. Both iodothyronine deiodinase and TR expression in the fetoplacental unit are fundamental in controlling active TH delivery to the fetus. Using real time RT-PCR and gene specific Taqman probes and primers, we quantified mRNA expression of the deiodinase enzymes D2 and D3, and TRalpha1, TRalpha2 and TRbeta1 in the absence and pr...

Maternal thyroid hormones (THs) are important for fetoplacental development. We have previously reported lower fetal circulating concentration of THs in severe intrauterine growth restriction (IUGR) compared to gestationally-matched normal fetuses. The villous placental expression of TH receptors (TRs) and the TH transporter MCT8 is increased, whilst MCT10 expression is decreased, with severe IUGR.Objective: To assess the TH responsiveness of human cytot...

Thyroid hormones (TH) are important for the development of the fetus and placenta. Monocarboxylate transporter 8 (MCT8) is a potent plasma membrane TH transporter, present in the human placenta from 6 weeks of gestation. Its expression increases significantly with advancing gestational age. We postulate that MCT8 plays an important role in human placental development.Objective: To assess the effects of altered MCT8 expression on the survival, syncytialis...

Identifying the pathogenic pathways involved in complex diseases such as Graves’ disease (GD) has proved challenging. Although several genetic risk factors, including the HLA class II region, CTLA4, PTPN22 and CD25, encode molecules playing key roles in antigen presentation and controlling T cell recognition/signalling, the identification of novel susceptibility loci has the potential to provide further insights into disease pathogenesis. Recently gen...

Recently, linkage between chromosome 1q23 and rheumatoid arthritis within the Japanese population has been narrowed down to association of four single nucleotide polymorphisms (SNPs), fcrl3_3, fcrl3_4, fcrl3_5 and fcrl3_6, within FCRL3, a known regulator of B cell signalling. Of these four SNPs, fcrl3_3 was shown to disrupt FCRL3 expression on B cells, suggesting a potential etiological role. Association of fcrl3_3 was also replicated in a Japanese Graves’ disease ...

We have previously shown PTTG binding factor (PBF) to be a transforming gene both in vitro and in vivo, forming colonies in soft agar and tumours in nude mice. We have found that along with PTTG, PBF is upregulated in thyroid cancer and is also a prognostic indicator for recurrence. As our cohort of thyroid cancers showed significantly reduced sodium iodide symporter (NIS) expression compared to normal thyroid (47% reduction, N=27, P=0.005), which was negatively ...

During early development, the extravillous and villous placenta form by a process of proliferation and differentiation resulting in invasion of the uterine decidua and myometrium. The invasion of tissues during placentation is a model for the proliferative and invasive processes which occur during tumourogenesis. Pituitary tumor transforming gene (PTTG) interacts with a binding factor PBF, and PTTG expression correlates with tumor invasiveness in many neoplasms. We hypothesise...

Intrauterine growth restriction (IUGR) is a significant cause of perinatal morbidity, in particular neurodevelopmental delay, and is associated with fetal hypothyroxinemia. Thyroid hormone is essential for the optimal development of the central nervous system (CNS) in the fetus. Transport of the active ligand triiodothyronine (T3) across the cell membrane is required for its biological effects, initiated by binding of T3 to nuclear thyroid receptors (TR). Recently, the membran...

Angiogenesis is the rate-limiting step in tumour progression and metastatic spread. Both promoters and inhibitors of angiogenesis have been implicated in thyroid tumourigenesis. We have reported PTTG overexpression in thyroid and other cancers, and PTTG upregulation of the angiogenic factors FGF-2 and VEGF in vitro. To investigate whether PTTG also transactivates other downstream angiogenic effectors, we employed angiogenesis-specific cDNA arrays. Primary thyroid cells and PTT...

Chromosomal instability (CIN) is a common feature of many malignancies including papillary and follicular thyroid cancer. During mitosis, there are multiple stages which, if dysregulated, may result in CIN. One critical stage is the regulation of sister-chromatid separation at the metaphase-anaphase transition. Three key protein complexes regulate this process: separase, cohesins and securin (also known as pituitary tumor transforming gene). In vivo, most tumours studied demon...