Searchable abstracts of presentations at key conferences in endocrinology

ea0028p307 | Steroids | SFEBES2012

Adipose depot specific regulation of insulin signalling by glucocorticoids

Gathercole Laura , Morgan Stuart , Bujalska Iwona , Nasiri Maryam , Stewart Paul , Tomlinson Jeremy

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

ea0028p308 | Steroids | SFEBES2012

Negative regulation of 11β-HSD1 by GH in key metabolic tissues may contribute to metabolic disease in GH deficient patients

Morgan Stuart , Berryman Darlene , List Edward , Lavery Gareth , Kopchick John , Stewart Paul

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing’s syndrome (glucocorticoid excess) - notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol, and thus amplifies local glucocorticoid action. We hypothesise that 11β-HSD1 expression is neg...

ea0025oc2.7 | Steroids | SFEBES2011

Depot specific differences in the sensitivity to glucocorticoid and insulin action in human adipose tissue

Gathercole Laura , Hauton David , Morgan Stuart , Bujalska Iwona , Stewart Paul , Tomlinson Jeremy

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Differences in gene expression between omental (om) and subcutaneous (sc) adipose have been described, but molecular mechanisms underpinning differences in adipose biology are not known. Patients with glucocorticoid excess, Cushing’s syndrome, develop a phenotype characterized by central obesity. We have characterized the regulation of lipogenesis by gluco...

ea0025p118 | Cytokines, growth factors, neuroendocrinology and behaviour | SFEBES2011

Impact of synovial fibroblasts on adipose tissue

Hussain Ahkeb , Hardy Rowan , Patel Pushpa , Ahassan Mohammad , Filer Andrew , Stewart Paul , Cooper Mark

Rheumatoid arthritis (RA) is associated with a loss of lean mass and a corresponding increase in fat mass. How fat accumulation in RA is linked to synovial inflammation is unknown. Wnts comprise a family of secreted glycoproteins that are crucial in regulating adipocyte proliferation, apoptosis and differentiation. Recently we demonstrated that endogenously generated glucocorticoids (GCs) alter the pattern of wnt secretion by synovial fibroblasts (SFs), favouring production of...

ea0025p229 | Pituitary | SFEBES2011

20 year experience in the surgical management of cushing’s disease in a UK tertiary referral centre

Hassan-Smith Zaki , Johnson Alan , Toogood Andrew , Arlt Wiebke , Sherlock Mark , Stewart Paul

Objective: The past 2 decades have seen advances in the surgical management of Cushing’s disease (CD). Our aim was to meet the need for current data on clinical features, long-term outcomes, and prognostic indicators.Patients and methods: We conducted a retrospective study of 71 patients treated by trans-sphenoidal surgery (TSS) for CD. All patients were operated on by the same surgeon in a single centre between 1988–2009. Diagnosis was confirm...

ea0025p294 | Steroids | SFEBES2011

Cortisol decreases lipogenesis in human hepatocytes

Nasiri Maryam , Gathercole Laura , Hauton David , Morgan Stuart , Bujalska Iwona , Stewart Paul , Tomlinson Jeremy

Glucocorticoid (GC) excess (Cushing’s syndrome) is characterized by central obesity, insulin resistance and in up to 20% of cases, non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive spectrum of disease ranging from hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Many processes contribute to lipid accumulation within heaptocytes including de novo lipogenesis which includes the rate-limiting carboxylation of acetyl CoA to malonyl-CoA by a...

ea0021oc1.7 | Diabetes and metabolism | SFEBES2009

Prospective changes in glucocorticoid metabolism predict alterations in metabolic phenotype

Gray Joanna , McCarthy Theresa , Hughes Susan , Hughes Beverly , Stewart Paul , Tomlinson Jeremy

Glucocorticoid (GC) production rates are elevated in obese, insulin resistant individuals. We and others have demonstrated decreased hepatic cortisol regeneration through reduced 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity that converts inactive cortisone to cortisol. In addition, there is enhanced cortisol clearance by A-ring reductases, (notably 5α-reductase). We have argued that these changes drive the hypothalamo-pituitary–adrenal axis a...

ea0021oc3.8 | Young Endocrinologists prize session | SFEBES2009

Identification and functional impact of novel mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 1 in patients with hyperandrogenism

Lawson Alexander , Walker Elizabeth , Lavery Gareth , Bujalska Iwona , Hughes Beverly , Arlt Wiebke , Ride Jonathan , Stewart Paul

In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the reduction of cortisone to cortisol within the endoplasmic reticulum. For functional 11-ketoreductase activity, 11β-HSD1 requires the NADPH-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH). Loss of 11-ketoreductase activity results in increased cortisol clearance and activation of the HPA axis wi...

ea0021p168 | Diabetes and metabolism | SFEBES2009

Glucocorticoid and insulin regulation of lipid metabolism in human adipocytes

Gathercole Laura , Bujalska Iwona , Morgan Stuart , Hauton Dave , Stewart Paul , Tomlinson Jeremy

Patients with glucocorticoid excess develop a phenotype characterized by central obesity, however, the impact of glucocorticoids upon the processes that regulate lipid accumulation has not been fully explored. We hypothesize that intracellular generation of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1) is an important regulator of lipid metabolism.In adipocytes, acetyl-CoA carboxylase 1 and 2 (ACC1/2) convert acetyl-CoA to ...

ea0021p362 | Steroids | SFEBES2009

MicroRNA expression profiling of non-tumorous adrenal tissue and modulation of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes by miR-24

Wood Stacy , MacKenzie Scott , Stewart Paul , Fraser Robert , Connell John , Davies Eleanor

The CYP11B1 and CYP11B2 genes encode 11β-hydroxylase and aldosterone synthase, which catalyse the production of cortisol and aldosterone, respectively, and have been implicated in the development of hypertension. For this study, we wished to investigate the role of microRNAs (miRNAs), a novel class of post-transcriptional gene regulators. To that end, we generated a profile of human adrenal miRNAs to study, and then investigated the action of one adrenal miR...