Endocrine Abstracts

Thyroid cancer accounts for ca. 90% of all endocrine tumours and ca. 60% of endocrine cancer deaths, with an increasing incidence of the disease worldwide. Disease recurrence and metastasis occur in up to 20% of patients. Many of the tumour-initiating events of thyroid cancer have already been identified. Overexpression of Galectin-3 and telomerase, point mutations in RAS and BRAF, rearrangements of the PAX8-PPAR gamma and RET genes have all been implicated in thyroid tumour i...

We have previously shown Pituitary Tumor Transforming Gene (PTTG) and basic Fibroblast Growth Factor (FGF-2) to be upregulated in thyroid cancer. PTTG requires interaction with the protein PBF (PTTG Binding Factor) to stimulate FGF-2 secretion, and hence promote tumour angiogenesis and growth. We now report that PBF is also upregulated in hyperplastic and neoplastic thyroid tissues compared with normal thyroid (N=11) (2.6-fold in multinodular goitre (N=25, P=0.002), and 3.3-fo...

During mitosis, temporal release of separase from its inhibitor securin results in cohesin cleavage, thereby promoting anaphase. The developing fetal brain has rapidly proliferating neuronal cells whilst adult neurons no longer proliferate. When comparing 61 fetal and 12 adult human brain samples, we found significantly increased separase mRNA and protein throughout ontogeny and reduced securin expression in fetal brain compared with adult. Using MTT assays, we examined the ef...

The vulnerability of early central nervous system (CNS) development to thyroid hormone (TH) deprivation has been highlighted by studies showing an association between maternal hypothyroxinemia during the first trimester and long-term neurodevelopmental delay in the offspring. The molecular mechanisms underlying this observation are, however, poorly understood. It is known that the actions of triiodothyronine (T3), the active TH metabolite, are primarily mediated by TRs, which ...

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...

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...