Endocrine Abstracts

Overt hypothyroidism, diagnosed and treated with L-thyroxine pre-pregnancy, affects 1% of pregnancies. Untreated maternal hypothyroidism is associated with adverse obstetric and neonatal outcomes, and even when partially treated the risks of miscarriage and prematurity remain elevated compared to euthyroidism. With increased understanding of the normal physiological changes to thyroid function during pregnancy, there should be a predictive approach to thyroxine ...

The transplacental passage of thyroid hormones (TH) from the maternal to fetal circulations is important for normal fetal development, particularly the fetal central nervous system. This is particularly so before the onset of endogenous fetal TH production from the second trimester of pregnancy. The human hemochorial placenta regulates the quantity of TH passing through and the complement of the different forms of TH to ensure requisite levels are present in the fetus for each...

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 ...

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...

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...

The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in h...

Background: Radiotherapy is the mainstay of NPC (nasopharyngeal carcinoma) treatment and recently there is increased use of concurrent chemo-irradiation (CCRT) to improve survival. The irradiation field for NPC includes the base of skull, risking radiation damage to the hypothalamic–pituitary (HP) axis.Aims: To evaluate the prevalence of HP dysfunction in NPC survivors post-irradiation and to compare the risk of developing HP dysfunction amongst pat...

Mutations in the plasma membrane thyroid hormone (TH) transporter, MCT8, are associated with severe global neurological deficits accompanied by abnormal circulating TH levels. We have previously shown that MCT8 over-expression in human neuronal precursor cells (NT2) increases cellular T3 uptake and reduces proliferation.Objectives: To quantify and localise the expression of MCT8 in human fetal CNS and to investigate the role of MCT8 in NT2 neurodifferent...

Human securin, also known as pituitary tumor transforming gene, plays a critical role during cell division. Ubiquitination of securin during the metaphase to anaphase transition releases its binding partner separase, which cleaves the cohesins holding sister chromatids together. We recently demonstrated reduced securin expression in human fetal versus adult brain, and dissected its role in affecting the proliferation of human embryonal CNS precursor NTERA-2 (NT-2) cells. We ha...