Searchable abstracts of presentations at key conferences in endocrinology

ea0013p261 | Reproduction | SFEBES2007

Measurement of peak and trough testosterone levels during treatment with Testogel

Smith RH , Karavitaki N , Walker N , Wass JAH

Background: A variety of preparations for testosterone replacement therapy are currently available. Testogel, a transdermal gel, is widely used and considered one of the most convenient. Measurement of serum testosterone level at various times after application of the gel is regarded as one of the ways of monitoring response to treatment.Aim: To investigate the variability of testosterone absorption and whether testosterone levels prior to application of...

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...

ea0005p81 | Diabetes, Metabolism and Cardiovascular | BES2003

Effects of the 11beta hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in human obesity

Sandeep T , Andrew R , Homer N , Walker B

Inhibiting 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) has been proposed to prevent local regeneration of cortisol from cortisone, and thus enhance hepatic and adipose insulin sensitivity. In healthy men and patients with type 2 diabetes, the non-selective 11HSD inhibitor carbenoxolone enhances hepatic insulin sensitivity but, paradoxically, does not increase peripheral glucose disposal. In obesity, 11HSD1 activity and mRNA are increased in adipose biopsies. We tested ...

ea0007oc36 | Diabetes and metabolism | BES2004

Tissue-specific alterations of glucocorticoid metabolism in ob/ob mice

Livingstone D , Packer S , Kerr R , Morton N , Walker B , Andrew R

Glucocorticoid metabolism is altered in a tissue-specific manner in obesity. Increased reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) amplifies glucocorticoid action in abdominal fat, whereas increased metabolism of glucocorticoids by hepatic A-ring reductases may contribute to activation of the hypothalamic-pituitary-adrenal axis. These changes have been characterised in leptin-resistant obese Zucker rats and obese humans. Here we inves...

ea0007p240 | Thyroid | BES2004

Defining aetiological variants within the HLA class II region that lead to the development of Graves' disease

Simmonds M , Heward J , Howson J , Cordell H , Walker N , Todd J , Franklyn J , Gough S

Genetic variants of the HLA class II region (DRB1, DQB1 and DQA1) and CTLA-4 contribute to susceptibility to Graves' disease (GD). Whilst disease susceptibility has been mapped to a non-coding 6.1kb 3' region of CTLA-4, the primary aetiological variants within the HLA class II region remain unknown. The aims of this study were (i) determine which of the three HLA class II loci account for the primary association with GD and (ii) examine disea...

ea0005p236 | Steroids | BES2003

Regulation of the human 11beta-hydroxysteroid dehydrogenase gene by glucocorticoids

Bedendo O , Bujalska I , Draper N , Walker E , Hewison M , Mantero F , Stewart P

Glucocorticoids regulate transcription of many genes through the binding to the glucocorticoid receptor (GR) however, their intracellular levels are tightly regulated by the microsomal enzyme 11beta-hydroxysteroid dehydrogenase. Two isozymes of this enzyme have been cloned and characterised; 11beta- hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which is mainly expressed in the liver and adipose tissue and 11beta-HSD type 2 expressed in the kidney and placenta. Within 2.5kb...

ea0009p156 | Thyroid | BES2005

Regression mapping of the HLA association with Graves' disease

Simmonds M , Howson J , Heward J , Cordell H , Foxall H , Carr-Smith J , Gibson S , Walker N , Tomer Y , Franklyn J , Todd J , Gough S

Graves' disease (GD) is caused by genetic and environmental factors. To date only the HLA class II region on chromosome 6p21 and the CTLA-4 gene on chromosome 2q33 have been consistently associated with disease. A recent study has indicated the most likely position of the aetiological variant in the CTLA-4 locus to be in a 6.1kb region of the 3' untranslated region of the gene. However the same degree of mapping resolution has not been achieved for the HLA class II region due ...

ea0005oc22 | Obesity and Diabetes | BES2003

Defining the molecular basis for apparent cortisone reductase deficiency reveals a novel redox potential mechanism within the endoplasmic reticulum

Draper N , Walker E , Bujalska I , Tomlinson J , Chalder S , Bedendo O , Mason P , Laing I , Ray D , Malunowicz E , Connell J , Hewison M , Stewart P

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) catalyses the interconversion of hormonally active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an NADP(H) dependent enzyme expressed in human liver and adipose that is targeted to the ER membrane with a lumenal catalytic domain. In vivo the enzyme acts predominantly as a reductase, generating F from E. The inherited condition, Apparent Cortisone Reductase Deficiency (ACRD) is a form of PCOS characterised by ACTH medi...