Searchable abstracts of presentations at key conferences in endocrinology

ea0011p334 | Diabetes, metabolism and cardiovascular | ECE2006

Regulation of hexose-6-phosphate dehydrogenase (H6PDH) in human fetal liver WRL-68 cells

Swali A , Bujalska I , Stewart PM , Walker EA

Excessive glucocorticoid exposure has been implicated in the pathogenesis of obesity and the metabolic syndrome. The in vivo conversion of inactive to active glucocorticoids is catalysed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), requiring NADPH as a cofactor. Hexose-6-phosphate dehydrogenase (H6PDH) is co-localised with 11β-HSD1 in the lumen of the endoplasmic reticulum and controls local NADPH availability. Thus H6PDH plays an important role...

ea0029p1225 | Obesity | ICEECE2012

Effect of secreted frizzled-related protein 2 (sFRP2) from adipose tissue on pancreatic cell function

Bujalska I. , Rabbitt E. , Gathercole L. , Stewart P.

The detrimental effect of excessive obesity on insulin resistance is well established. The expansion of adipose tissue is dependent on two processes: adipogenesis and angiogenesis and the Wnt signalling pathway has been reported to affect both. In adipose tissue the Wnt signalling pathway functions in a converse manner: increasing commitment of mesenchymal stem cells to preadipocytes and inhibiting differentiation of preadipocytes to mature adipocytes by decreasing expression ...

ea0009oc3 | Oral Communication 1: Diabetes and metabolism | BES2005

Depot specific glucocorticoid regulation of key components of the insulin signalling cascade in human adipose tissue

Gathercole L , Bujalska I , Stewart P , Tomlinson J

Glucocorticoid excess, Cushing's syndrome, is a recognised cause of insulin resistance and in some cases diabetes mellitus. In addition, patients develop reversible central obesity. However, the exact mechanisms that underpin the development of glucocorticoid mediated insulin resistance and central obesity are not known. We have hypothesized that at a cellular level, the tissue specific generation of cortisol from inactive cortisone through the action of 11beta-hydroxysteroid ...

ea0009p15 | Diabetes and metabolism | BES2005

Prostaglandin synthesis in adipose tissue from women with simple obesity - differences between omental and subcutaneous depots

Quinkler M , Bujalska I , Tomlinson J , Smith D , Stewart P

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis and its product, prostaglandin (PG) H2 is a precursor of PGE2, PGF2, PGD2 and PGI2. PGH2 is also metabolised by prostaglandin D-synthase (PTGDS) to PGD2 which spontaneously converts to PGJ2 or can be enzymatically converted to PGF2alpha by AKR1C3. These two metabolites have opposite effect on adipogenesis; PGF2alpha is a PPARgamma antagon...

ea0009p84 | Endocrine tumours and neoplasia | BES2005

DNA array analysis of a vitamin D-resistant variant of MCF-7 breast cancer cells

Townsend K , Colston K , Bujalska I , Campbell M , Hewison M

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3) is a potent antiproliferative agent with putative applications in the treatment of common cancers. However, doses of 1,25D3 required to achieve tangible anticancer responses also stimulate unwanted calciotropic effects. Data suggest that this is due, in part, to acquired resistance to 1,25D3 in cancer cells, particularly in more aggressive tumours. To investigate this fu...

ea0007p219 | Steroids | BES2004

Hexose 6-phosphate dehydrogenase expression confers reductase activity upon 11 beta-HSD1 in adipose tissue

Bujalska I , Tomlinson J , Draper N , Walker E , Stewart P

Glucocorticoids are an important adipogenic factor. In man, circulating cortisol excess causes visceral obesity, but in simple obesity glucocorticoid levels are usually normal. However, in adipose tissue cortisol availability to bind to the glucocorticoid receptor (GR) is modulated by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). Human preadipocytes display both dehydrogenase (cortisol to cortisone) and oxo-reductase (cortisone to cortisol) activity. Recent genet...

ea0005p141 | Endocrine Tumours and Neoplasia | BES2003

Abnormal expression of 11beta-hydroxysteroid dehydrogenase 2 in primary cultures of human pituitary adenomas

Rabbitt E , Bujalska I , Stewart P , Hewison M , Gittoes N

Glucocorticoids (GCs) mediate many of their physiological effects through inhibition of cell proliferation. More contentious is the antiproliferative action of GCs and their possible tumour-modifying effects in neoplastic tissues. However, in recent studies we have shown that 'prereceptor' metabolism of GCs by the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is a pivotal determinant of cell proliferation and tumour formation. Two isozymes of 11beta-HSD interconvert ...

ea0005p216 | Steroids | BES2003

Adipocyte size increases with BMI, but is unrelated to 11 beta-hydroxysteroid dehydrogenase type 1 expression

Tomlinson J , Bujalska I , Collard M , Stewart P

Patients with Cushing's syndrome develop florid, but reversible central obesity. However, circulating cortisol levels are not elevated in simple obesity. Within human adipose tissue, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is highly expressed and converts inactive glucocorticoid, cortisone to active cortisol. Rodents over-expressing 11beta-HSD1 in adipocytes develop central obesity exclusively as a result of increased adipocyte size. Whilst it has ...

ea0005p226 | Steroids | BES2003

Identification of glucocorticoid target genes in human subcutaneous and omental adipose tissue using microarray analysis

Bujalska I , Montague C , Smith D , Stewart P

The central obese phenotype characteristic of Cushing's syndrome emphasises the role of glucocorticoids (GC) in regulating adipose tissue mass and distribution. We have shown that GCs stimulate adipocyte differentiation, but equally inhibit adipose stromal cell (ASC) proliferation. These effects are regulated at a pre-receptor level through 11beta-hydroxysteroid dehydrogenase type 1, but the 'post-receptor' signalling pathways remain unclear. To define novel GC targets in huma...

ea0003oc38 | Hormone Action | BES2002

Autocrine generation of androgens within adipose tissue: Implications for polycystic ovarian syndrome (PCOS)

Sinha B , Tomlinson J , Bujalska I , Hewison M , Stewart P

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabo...