Endocrine Abstracts

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...

High protein diets suppress appetite, but are difficult to adhere to. Understanding how the gut senses protein may identify mechanisms to drive satiety. Amino acid products of protein digestion are thought to be sensed by G protein coupled receptors in the gut, including the calcium sensing receptor (CaSR). Calcium ions are the major ligand of the CaSR, but aromatic amino acids, particularly L-phenylalanine (L-Phe), allosterically modulate CaSR activity....

Despite extensive genomic profiling a better understanding of the contributory factors that promote aggressive thyroid cancer is urgently needed. The proto-oncogenes PBF and PTTG have been implicated in thyroid cancer but there is a lack of information regarding their co-expression and specific roles in tumour progression. Separate studies have previously indicated that PBF and PTTG may disrupt pathways associated with the tumour suppressor p53 that are central to DNA-damage r...

PBF is a multifunctional proto-oncogene overexpressed in thyroid and other endocrine cancers. Previously we identified a functional interaction between PBF and the tumour suppressor p53 in well-differentiated thyroid cancer (WDTC). Here, we delineate the oncogenic mechanisms of PBF, along with its binding partner PTTG, in head and neck cancer (HNSCC), in which TP53 mutations (mutTP53) are common (>50%). HNSCC tissue revealed significant upregulation of PBF and PTTG mRNA (&...

Patients termed to have radioiodine-refractory differentiated thyroid cancer (RR-DTC) cannot accumulate sufficient radioiodine for a therapeutic response due to sodium iodide symporter (NIS) dysregulation via diminished expression and/or altered plasma membrane (PM) localisation. Currently, the regulation of NIS localisation remains poorly defined and despite protein-protein interactions being well-described to modulate trafficking events, the NIS interactome is limited. Previ...

Introduction: Heavy menstrual bleeding (HMB) affects over 1 million women in the UK. At menses, progesterone (P4) withdrawal drives inflammation, tissue break-down and repair of the endometrium. Glucocorticoids are mediators of inflammation and angiogenesis. Our previous studies have demonstrated that differential endometrial expression of the glucocorticoid-metabolising enzymes, 11β-HSD-1 and -2, may play a role in HMB. We hypothesise that aberrant lo...

Human sulfation depends on provision of the universal sulfate donor PAPS by the two PAPS synthase isoforms PAPSS1 and PAPSS2. Mutations in PAPSS2 have been identified as a monogenic cause of androgen excess presenting with premature adrenarche and polycystic ovary syndrome, due to decreased sulfation of the androgen precursor DHEA by DHEA sulfotransferase (SULT2A1) and hence increased conversion of DHEA to active androgens (New Eng J Med 2009 360 (22)...

The role of the thyrotropin receptor (TSHR) in bone is unclear. TSHR-deficient mice have low bone mineral density (BMD) and focal osteosclerosis despite normal thyroid hormones (suggesting TSHR function, in bone, is important). Subclinical hypothyroidism (SH) has various aetiologies including thyroid autoimmunity (TA) and inactivating TSHR mutations (TSHR-M). In TSHR-deficiency & TSH-M elevated TSH compensates for reduced TSHR function, whereas in TA it compensates for red...

Objectives: Transition from paediatric (PC) to adult diabetes care (AC) is a vulnerable period for young people (YP). The West Midlands (WM) Regional Paediatric Diabetes Network conducted a region-wide study of Diabetes transition outcomes to identify 1. Areas of good practice, 2. Risk factors for poorer outcomes, 3. Regional objectives for services and 4. Provide baseline data against which future performance can be measured.Methods: Retrospective regio...

Abdominal surgery and diseases such as endometriosis cause persistent abdominal adhesions leading to pelvic pain, infertility and in severe cases, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (LOX) is a key enzyme required for crosslinking and deposition of insoluble collagen.10–12 weeks old female C57Bl/6 mice (3–10 mice per gro...