Searchable abstracts of presentations at key conferences in endocrinology

ea0025p179 | Endocrine tumours and neoplasia | SFEBES2011

Pro-opiomelanocortin is a marker of liver and brain metastases from small cell lung cancer xenografts

Meredith Suzanne , Babur Muhammad , Begum Ghazala , Telfer Brian , Gieling Roben , Dean Emma , Dive Caroline , Williams Kaye , White Anne

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...

ea0025p244 | Pituitary | SFEBES2011

BAC recombineering to understand the role of the alternative promoter in the regulation of prolactin expression

Awais Raheela , McNamara Anne , Harper Claire , Adamson Anthony , Spiller Dave , Semprini Sabrina , Mullins John , Davis Julian , White Michael R H

Alternative promoters control many genes including prolactin (PRL), which in man is expressed at extra-pituitary sites controlled by an alternative promoter located 5.8 Kbp upstream of the pituitary transcription start site. Previous studies using short promoter fragments may be misleading, as the human hPRL genomic locus has many conserved far-upstream regions. To study the function of the alternative promoter, we engineered a bacterial artificial chromosome (BAC) expressing ...

ea0021p293 | Pituitary | SFEBES2009

Long-term unsynchronised transcriptional cycles in individual living pituitary cells

Harper Claire , Finkenstadt Barbel , Woodcock Dan , Friedrichsen Sonke , Semprini Sabrina , Spiller Dave , Mullins John , Rand David , Davis Julian , White Mike

Gene expression in living cells is dynamic and unstable, and fluctuations in transcription may be subject to stochastic regulation of processes including transcription factor and polymerase recruitment, and chromatin remodelling. One gene that has been shown to display dynamically variable transcription and marked heterogeneity between cells is prolactin (PRL). Time-lapse imaging of PRL-reporter gene expression in single rat pituitary GH3 cells revealed distinct long-term tran...

ea0021p298 | Pituitary | SFEBES2009

Onset of prolactin gene transcription in nascent pituitary lactotroph cells

Featherstone Karen , Harper Claire , McNamara Anne , Semprini Sabrina , Spiller David , McNeilly Alan , Mullins John , White Michael , Davis Julian

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...

ea0021p299 | Pituitary | SFEBES2009

Immuno-modulatory role of prolactin in immune tissues driven by the alternative promoter

McNamara Anne , Awais Raheela , Semprini Sabrina , Harper Claire , Featherstone Karen , Spiller Dave , Davis Julian , Mullins John , White Mike

Prolactin (PRL) is a hormone mainly produced by the lactotroph cells of the anterior pituitary gland. Besides its pivotal role in reproduction, PRL has also been found to have immuno-modulatory properties. The pituitary is the main source of circulating PRL, however it is also expressed in humans at extra-pituitary sites1. In extra-pituitary tissues, PRL mRNA contains an extra exon (exon 1a), and expression is regulated by an alternative promoter upstream of the pit...

ea0019p11 | Bone | SFEBES2009

Impact of body mass index at baseline on parathyroid hormone and phospho-calcium metabolism in adult growth hormone deficient patients before and after growth hormone replacement therapy

Mon Aung , Ahmad Aftab , Malipatil Nagaraj , Joseph Franklin , White Helen , Joshi Ashwin , Sharma Dushyant , Fraser William , Vora Jiten

Background: Adult growth hormone deficient (AGHD) is associated with reduced bone turnover and reduced bone mineral density (BMD): factors improved by growth hormone replacement (GHR). Obesity is associated with reduced bone turnover but increased BMD. We investigated the impact of body mass index on parathyroid hormone (PTH), phospho-calcium metabolism and bone turnover in AGHD patients before and after GHR.Study design: Of 31 AGHD patients (15 obese pa...

ea0013oc38 | British Thyroid Association Award | SFEBES2007

The novel thyroid hormone derivative 3-iodothyronamine increases food intake via the hypothalamic arcuate nucleus

White Nicholas , Dhillo Waljit , Bewick Gavin , Gardiner James , Scutt James , Thompson Emily , Kokkinos Alexander , Armstrong Alan , Ghatei Mohammad , Bloom Stephen

3-iodothyronamine (T1AM) is a novel, endogenous rapid acting biogenic amine, which is a potent agonist of the G-protein coupled trace amine-associated receptor 1, TAAR1. It has been suggested that endogenous T1AM could be generated by enzymatic deiodonation and decarboxylation of T4. The presence of T1AM in rat brain and the distribution of the TAAR1 receptor in the hypothalamus suggest that T1AM may affect food intake and regulate e...

ea0011s58 | Steroid hormone receptors | ECE2006

The ups and downs of nuclear receptor action in fat and fertility

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

Nuclear Receptors control many developmental and physiological processes by regulating the expression of networks of genes. Their ability to activate or repress gene transcription depends on the recruitment of coactivators and corepressors that function as scaffolds for the binding of chromatin remodelling enzymes. RIP140 is a ligand dependant corepressor for most, if not all, nuclear receptors with key roles in energy homeostasis and reproduction.RIP140...

ea0009oc6 | Oral Communication 1: Diabetes and metabolism | BES2005

Analysis of post-translational processing and trafficing of agouti-related protein

Pritchard L , Creemers J , Gyte A , Davies N , Le Rouzic P , Lawrence C , Luckman S , Brennand J , White A

Agouti-related protein (AGRP) plays a key role in energy homeostasis with the carboxy-terminal domain acting as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, allowing it to regulate local concentrations of AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. However, AGRP contains several consensus prohormone convertase cleavage sites: Lys52-Lys...

ea0003p5 | Bone | BES2002

Changes in parathyroid hormone sensitivity and rhythmicity and its effects on bone metabolism following growth hormone replacement in adult growth hormone deficient patients

Ahmad A , White H , Thomas J , Clewes A , Hopkins M , Guzder R , Ibrahim H , Durham B , Vora J , Fraser W

BACKGROUND: Adult Growth Hormone Deficiency (AGHD) is associated with reduced bone mineral density (BMD). PTH plays an important role in bone metabolism and reports have suggested target cell insensitivity to PTH as a contributor to the changes in bone turnover seen in AGHD. Although growth hormone replacement (GHR) increases BMD, the underlying mechanisms remain unclear.OBJECTIVES: To determine the effect of GHR on 24-hour PTH profiles, phosphocalcium ...