Endocrine Abstracts

The overproduction of ACTH, in conditions such as Congenital Adrenal Hyperplasia (CAH) leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment that would directly block ACTH action. Such a therapy, especially one that can be orally administered, would be of great clinical value allowing a ‘block and replace’ tre...

Type 1 diabetes mellitus (T1DM) not only is congenital disease that known as insulin-dependent diabetes, often occurs in children and adolescents. Recent advances in quantitative proteomics including fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) have offered opportunities to discover plasma proteins as biomarkers for tracking the progression and for underst...

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...

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...

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...

The importance of thyroid hormone (TH) transporters to central nervous system (CNS) development has been highlighted by reports of severe global neurological impairment associated with mutations in the potent TH transporter, MCT8. Even subclinical maternal hypothyroidism in early pregnancy has been associated with long-term neurodevelopmental delay in the offspring suggesting that TH is crucial for early fetal brain development. The cellular entry of TH requires the function o...

The key mitotic regulator pituitary tumor transforming gene (PTTG) is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We examined the function and expression of PTTG’s interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with PTTG. In contrast to PTTG, the cleaved forms of separase and Rad21 were hi...

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...

Human securin, known also as pituitary tumor transforming gene (PTTG), has established oncogenic and cell regulatory functions. PTTG transforms cells in vitro, inhibits sister chromatid separation and regulates secretion of fibroblast growth factor-2 (FGF-2). FGF-2 is a key regulator of CNS development and PTTG/securin expression has previously been reported in murine fetal brain. We examined mRNA and protein expression of PTTG and FGF-2 in 35 first trimester (7-12 weeks) and ...

Olfactory marker protein (OMP) is a marker of olfactory receptor-mediated chemoreception, even outside the olfactory system. Here, we report that OMP expression in the pituitary gland plays a role in basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) production and secretion. We found that OMP was expressed in human and rodent pituitary glands, especially in PRL-secreting lactotrophs. OMP knockdown in GH4 rat pituitary cells increased PRL production and secr...