Searchable abstracts of presentations at key conferences in endocrinology

ea0019p334 | Steroids | SFEBES2009

GR is hyperphosphorylated during mitosis and associates with the mitotic spindle

Matthews L , Spiller D , Rivers C , Norman M , White M , Ray D

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. Previous studies have demonstrated altered Gc sensitivity during mitosis. This reduced sensitivity can be explained only in part through the selective export of GR in mitotic cell populations. In this study ligand-independent, cell cycle-dependent effects on GR have been explored.Mitotic cells show a marked increase in ligand-independent ser211 ...

ea0018p31 | (1) | MES2008

Diagnostic cut-off for calcitonin: is 10 ng/l still valid?

Ramachandran Radha , Benfield Patricia , White Sara , Chapman Richard , Meeran Karim , Donaldson Mandy , Martin Niamh

Aim: Population studies have shown that basal calcitonin concentrations are below 10 ng/l in the normal population. Ten nanograms per liter is used as a diagnostic cut-off by most laboratories and patients with levels higher than this are offered a pentagastrin stimulation test to exclude medullary thyroid carcinoma. However, these guidelines were adopted from studies that used the Cisbio Immunoradiometric assay for measuring calcitonin. Most laboratories have now moved to che...

ea0015oc32 | Pituitary, disease | SFEBES2008

Coupling of GR cellular distribution and function to the cell cycle

Matthews Laura , Spiller David , Rivers Caroline , Norman Michael , White Michael , Ray David

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. GR is a ligand-activated transcription factor which mediates effects within the nucleus or cytoplasm to regulate genomic or non-genomic events. Localisation of the GR to a specific cellular compartment is therefore an important determinant of the cellular response to Gcs.Live cell imaging of GR trafficking in cells transfected with fluorophore-t...

ea0013oc25 | Neuroendocrinology, reproduction and cardiovascular | SFEBES2007

Manipulation of proprotein convertase 1 expression in AtT20 cells changes proopiomelanocortin processing and trafficking: Implications for ACTH regulatory pathways

Day Tom , Warhurst Anne , Oliver Robert L , Pritchard Lynn E , White Anne

We have previously shown that the ACTH precursor, POMC, is present in human plasma and is the predominant secreted POMC peptide. This suggests that POMC processing is incomplete in neuroendocrine cells and regulation of the post-translational cleavage pathway is important in controlling secretion of ACTH. We have therefore analysed the dynamics of POMC processing in both AtT20 pituitary adenoma cells and primary rat pituitary cells. In both cases, large quantities of POMC, as ...

ea0013oc30 | Neuroendocrinology, reproduction and cardiovascular | SFEBES2007

Consequences of variation in the CYP11B2 and CYP11B1 genes on hypothalamic-pituitary-adrenal axis activity

Freel E Marie , White Ann , Ingram Mary , Fraser Robert , Davies Eleanor , Connell John

Aldosterone is key in the development of hypertension. We have shown that a SNP (−344T) in the 5’ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) was associated with aldosterone excess and high blood pressure. However, the most robust phenotype is altered adrenal 11-hydroxylation efficiency (deoxycortisol to cortisol); a step carried out by 11β-hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B...

ea0013p232 | Neuroendocrinology and behaviour (including pituitary) | SFEBES2007

Relaxin-3 stimulates the stress axis

McGowan Barbara , Stanley Sarah , White Nick , Donovan Joe , Gardiner James , Ghatei Mohammad , Bloom Stephen

Relaxin-3 is a newly discovered member of the insulin superfamily. It is expressed in the nucleus incertus (NI) of the brainstem which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the G-protein-coupled receptors RXFP1 and RXFP3. RXFP3 is expressed predominantly in the CNS, and in particular within the hypothalamic paraventricular nucleus (PVN). The physiological function of relaxin-3 is unknown but recent work suggests it may play a role in appeti...

ea0012s9 | Novel regulation of orphan receptor function | SFE2006

The ups and downs of nuclear receptor action in metabolic tissues

Parker M , Kiskinis E , Christian M , Seth A , Debevec D , Nichol D , Steel J , White R

Nuclear receptors control developmental and physiological processes by regulating the transcription of gene networks in specific cells. This is achieved by the recruitment of coactivators and corepressors that lead to chromatin remodelling and alterations in gene transcription. RIP140 is a ligand dependant corepressor for nuclear receptors that plays key roles in adipose tissue and muscle to regulate energy homeostasis.RIP140 regulates carbohydrate and l...

ea0012s16 | New frontiers in steroid hormone metabolism | SFE2006

Hexose-6-phosphate dehydrogenase and glucocorticoid metabolism

Lavery GG , Chalder SM , Bujalska I , Parker KL , White PC , Stewart PM , Walker EA

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...

ea0012oc3 | Young Endocrinologist prize session | SFE2006

Co-administration of SR141716 with peptide YY or oxyntomodulin has additive effects on food intake in mice

White NE , Dhillo WS , Small CJ , Lui YL , Gardiner JV , Ghatei MA , Bloom SR

BackgroundSR141716 (Rimonabant) has been shown to significantly inhibit food intake and reduce body weight in rodents and humans by antagonising CB1 receptors. The gut hormones peptide YY3–36 (PYY3–36) and oxyntomodulin (OXM), released from L-cells in the small intestine inhibit food intake in both rodents and humans and this effect is thought to be mediated via the hypothalamus.Objective<...

ea0012oc22 | Pituitary, ovary and steroids | SFE2006

Coupling of cell cycle progression to GR cellular distribution

Matthews LC , Spiller DG , Rivers CA , Norman MR , White MRH , Ray DW

Glucocorticoids (Gcs) are important regulators of cellular homeostasis, with their effects mediated by the intracellular glucocorticoid receptor (GR). Once activated, the GR may initiate rapid effects within the cytoplasm, but also translocate to the nucleus to affect gene transcription. The subcellular localisation of the GR is therefore an important determinant in the cellular response to Gcs.To analyse subcellular trafficking of the GR, HeLa cells wer...