Endocrine Abstracts

Background: The identification of MRAP in 2005 as the first melanocortin-2-receptor (MC2R)/ACTH receptor accessory protein provided insight into the regulation of the melanocortin receptor system. Mutations in MRAP cause Familial glucocorticoid deficiency, an autosomal recessive disorder resulting in isolated cortisol deficiency. In vitro studies showed that MRAP was essential for the functional expression of the MC2R. The melanocortin receptor (MCR) family (MC1R to MC5...

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...

Thyroid hormones play a major role in the metabolic function of mammalian cells and are of particular importance in the development of the fetal brain. The MCT8 gene has recently been shown to encode an active and specific thyroid hormone transporter. Recent reports have identified mutations in the MCT8 gene in several unrelated boys presenting with severe X-linked psychomotor retardation and elevated serum T3.Ontogeny of mRNA encoding MCT8 was examined ...

During the metaphase to anaphase transition of mitosis, destruction of the human securin, pituitary tumor-transforming gene (PTTG), and subsequent activation of the cysteine endopeptidase separase, leads to the cleavage of RAD21, a component protein of the cohesin complex. The developing fetal brain has rapidly proliferating neuronal cells, whilst adult neurons no longer proliferate and are maintained in G0 status of the cell cycle. We have previously investigated the expressi...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from adrenal unresponsiveness to ACTH. Patients present in early childhood with hyperpigmentation, hypoglycaemic episodes and seizures secondary to glucocorticoid deficiency. If left untreated this condition is fatal. Mineralocorticoid production is normal. Mutations in the ACTH receptor have been well described and account for approximately 25% of cases. We describe 3 additional novel mut...

Glucocorticoids (GCs) play a fundamental role in the endocrinology of pregnancy but excess GC in utero may lead to IUGR. Protection against fetal exposure to GCs is provided by the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) located in the placental trophoblast. By contrast, relatively little is known concerning the function of GC-activating 11beta-HSD1 which is expressed within maternal decidua. We have used human deciduas (n=32 first, n=10 second and n=...

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: The hypothalamus-pituitary-adrenal axis (HPA) controls the neuroendocrine response to psychological and physiological stress. The balance of the hormones synthesised and secreted by these organs is tightly regulated. However, there are intrinsic differences in the relative expression of these hormones depending on sex, which can influence the magnitude of the endocrine response to stressors or the response to pharmacological treatments. Herein, we ...