Searchable abstracts of presentations at key conferences in endocrinology

ea0038oc3.3 | Steroids and adrenal | SFEBES2015

11β-HSD1-mediated decrease in COX2 expression is abrogated by hypoxia in human dermal fibroblasts

Tiganescu Ana , Wittmann Miriam , Morgan Ann , Stewart Paul

Chronic wounds contribute significantly to patient morbidity, mortality and associated healthcare costs. Glucocorticoid (GC) excess and hypoxia are both associated with impaired wound healing (WH) outcomes. The cyclooxygerase 2 (COX2) pathway is an integral component of inflammation and WH. Locally, GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates cortisol from inactive cortisone. Although we recently demon...

ea0034p268 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

H6PDH deficiency in muscle impacts amino acid metabolism

Zielinska Agnieszka , Doig Craig , Stewart Paul , Adamski Jerzy , Lavery Gareth

Hexose-6-phosphate dehydrogenase is an important factor in setting the redox status of the endo-/sarcoplasmic reticulum (ER/SR) lumen by generating the NADPH:NADP+ ratio for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediated glucocorticoid (GC) activation. H6PDH knockout mice (H6KO) clearly demonstrate the obligate nature of 11β-HSD1 for H6PDH, and display a vacuolating of type IIb fiber myopathy, elevated glycogen storage and type II to type...

ea0031p320 | Steroids | SFEBES2013

Glucocorticoids enhance insulin sensitivity in human hepatocytes

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

Patients with glucocorticoids (GC) excess develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. Current dogma suggests that GCs cause insulin resistance in all tissues. However, we have previously demonstrated that GCs induce insulin sensitisation in adipose tissue in vitro, whilst causing insulin resistance in skeletal muscle. In rodent hepatocytes, GCs enhance insulin stimulated lipogenesis but studies in human hepatocytes have not...

ea0028oc4.1 | Steroid | SFEBES2012

Increased 11β-hydroxysteroid dehydrogenase type 1 activity is associated with the adverse expression of glucocorticoid target genes in ageing human skin

Tiganescu Ana , Walker Elizabeth , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...

ea0028oc4.3 | Steroid | SFEBES2012

A hypomorphic H6PD allele is sufficient to rescue the skeletal myopathy but not the lack of 11β-HSD type 1-mediated glucocorticoid regeneration phenotypes of H6PDKO mice

Zielinska Agnieszka , Doig Craig , McCabe Emma , Stewart Paul , Lavery Gareth

In the endo/sarcoplasmic reticulum (ER/SR), hexose-6-phosphate dehydrogenase (H6PDH) generates an NADPH/ NADP ratio sufficient to drive 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid (GC) activation (11-DHC to corticosterone). In H6PDH knockout (H6PDKO) mice a reduced NADPH/NADP ratio leads to reversed 11β-HSD1 activity (corticosterone to 11-DHC), and GC insensitivity. They also display skeletal myopathy driven by activation of the un...

ea0028p333A | Steroids | SFEBES2012

Regulation of de novo lipogenesis in human liver by 5α-reductase

Nasiri Maryam , Gathercole Laura , Stewart Paul , Tomlinson Jeremy

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

ea0025p311 | Steroids | SFEBES2011

Hepatic 11β-hydroxysteroid dehydrogenase type 1 expression is dynamically related across the liver lobule and is linked to metabolic status

Ahmed Adeeba , Semjonous Nina , Rabbitt Elizabeth , Stewart Paul

Nearly all the functions of the liver display zonation in distribution within each the lobule. Hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1). Dysregulation of hepatic 11β-HSD1 activity has been implicated in insulin resistance. Key processes such as gluconeogenesis are located in the periportal hepatocytes, although current dogma describes hepatic 11&#94...

ea0021p180 | Diabetes and metabolism | SFEBES2009

Impact of glucocorticoids upon lipogenesis and β-oxidation in skeletal muscle

Morgan Stuart , Gathercole Laura , Stewart Paul , Smith Dave , Tomlinson Jeremy

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...

ea0021p349 | Steroids | SFEBES2009

Urinary steroid metabolite profiling in 11β-HSD1 and H6PDH transgenic mice

Semjonous Nina , Hughes Beverly , Walker Elizabeth , Lavery Gareth , Stewart Paul

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive glucocorticoid to their active form (cortisone to cortisol in humans, 11-dehydrocorticosterone (11-DHC) to corticosterone in mice), and is dependent upon the presence of cofactor NADPH generated by the enzyme hexose-6-phosphate (H6PDH) for its activity. The 11β-HSD1/H6PDH system is implicated in the pathogenesis of the metabolic syndrome by generating tissue specific glucocorticoid excess. The ...

ea0021p357 | Steroids | SFEBES2009

6-Phosphogluconate dehydrogenase: an NADPH-generating enzyme in the lumen of the endoplasmic reticulum

Bujalska Iwona , Ride Jonathan , Stewart Paul , Walker Elizabeth

6-Phosphogluconate dehydrogenase (6PGDH) is the third enzyme of the oxidative phase of the pentose phosphate pathway. The cytosolic form of this pathway is well characterised, but the details and significance of the endoplasmic reticulum (ER) version are only beginning to be understood. We have previously identified hexose-6-phosphate dehydrogenase (H6PDH), which catalyses the first two steps of this pathway within the lumen of the ER, as a pivotal regulator of ER reductases s...