Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0011p25 | Bone | ECE2006

Effects of growth hormone administration on parathyroid hormone sensitivity and bone mineral metabolism in established osteoporosis

Joseph F , Ahmad A , White HD , Joshi A , Durham B , Vinjamuri S , Ashawesh K , Fraser WD , Vora JP

Introduction: The beneficial effect of GH replacement on bone in AGHD patients is mediated by improvements in target organ sensitivity to PTH and phosphocalcium metabolism. In aging women with established osteoporosis, GH and IGF-1 concentrations are lower and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear.Methods: Fourteen postmenopausal women (63.4±2.1 years; mean BMD T score ± ...

ea0011p631 | Neuroendocrinology and behaviour | ECE2006

Pro-opiomelanocortin and ACTH, precursors of alphaMSH, are secreted from human melanocytes and keratinocytes and can stimulate melanogenesis

Rousseau K , Kauser S , Prtichard LE , Warhurst A , Oliver RL , Schmitz CA , Thody AJ , Tobin DJ , White A

Pro-opiomelanocortin (POMC) is endoproteolysed to ACTH and alpha MSH which bind to the melanocortin-1 receptor, (MC-1R), and act as principal mediators of human skin pigmentation. In addition there is increasing evidence that alpha MSH has important anti-inflammatory actions in the skin. The aim of this study was to determine the efficiency of processing and the involvement of the different peptides in melanogenesis. To address this question we utilized specific two-site immun...

ea0011p758 | Steroids | ECE2006

Mechanisms of human prolactin regulation by oestrogen

Adamson AD , Friedrichsen S , Semprini S , Wilding M , Harper CV , White MRH , Davis JRE

Oestrogens are capable of inducing rat prolactin gene transcription through liganded Oestrogen Receptor (ER) binding a degenerate oestrogen response element (ERE) sequence on the promoter 1440 bp upstream of the transcription start site. ER binding is thought to interact with DNA bound Pit-1 leading to chromatin looping bringing enhancer elements into proximity with the transcription start site. This ERE sequence, TGTCActaTGTCA, differs from the consensus GGTCAnnnTGACC by two ...

ea0011p763 | Steroids | ECE2006

Glucocorticoid receptors exert a profound anti-proliferative and anti-survival effect on human small cell lung cancer cells

Le Rouzic P , Gillingham H , Berry A , Kayahara M , Huynh T , Sommer P , White A , Ray DW

Glucocorticoids (Gcs) act via the glucocorticoid receptor (GR) to inhibit proliferation of many epithelial cell types, and induce apoptosis in others, notably lymphoblastic leukemia. Resistance to Gcs occurs in human small cell lung cancer (SCLC), manifest clinically as dysregulated secretion of ACTH-related peptides. Currently nothing is known of the biological consequences such resistance causes. We have previously shown that a panel of human SCLC cell lines secrete ACTH rel...

ea0009oc20 | Oral Communication 3: Neuroendocrinology | BES2005

Transcriptional activation of the prolactin gene by TNF-alpha is mediated via NFkB

Friedrichsen S , Wilding M , Harper C , Nelson G , Spiller D , White M , Davis J

The neuroendocrine and immune systems are closely linked, and cytokines such as IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), secreted by immune cells or neighbouring pituicytes, may have important local effects on pituitary function to modulate endocrine mechanisms of regulation.We have analysed the transcriptional regulation of the human prolactin (hPRL) gene promoter by TNF-alpha. Using stably transfected GH3 cells expressing luciferase und...

ea0009p3 | Diabetes and metabolism | BES2005

Low insulin-like growth factor-II (IGF-II) concentration predicts weight gain in normal weight subjects with type 2 diabetes

Heald A , Karvestedt L , Anderson S , McLaughlin J , Knowles A , Wong L , White A , Brismar K , Gibson M

IntroductionInsulin-like growth factors-I (IGF-I) and -II (IGF-II) are important in regulation of metabolism and growth. We previously reported in normal weight normoglycaemic individuals that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of abnormal glucose tolerance.MethodIn 224 type 2 diabetes subjects we assessed the ...