Searchable abstracts of presentations at key conferences in endocrinology

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...

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...

ea0021p363 | Steroids | SFEBES2009

Is increased 11β-HSD1 expression a key factor underpinning intrinsic and extrinsic skin aging?

Tiganescu Ana , Mayes Andrew , Hardy Rowan , Stewart Paul , Walker Elizabeth

Glucocorticoids are highly detrimental to skin integrity and function both when used locally for anti-inflammatory treatments and during conditions of raised systemic concentrations such as Cushing’s syndrome. Many of the adverse effects of glucocorticoids on skin are also symptoms associated with natural intrinsic aging and extrinsic photoaging.Locally, glucocorticoid availability is regulated independently of circulating levels by 11β-hydroxy...

ea0015p327 | Steroids | SFEBES2008

A paracrine role for 11β-hydroxysteroid dehydrogenase type 1 and glucocorticoids in the murine pancreatic islet

Swali Angelina , Tomlinson Jeremy , Walker Elizabeth , Stewart Paul

Type 2 diabetes manifests when pancreatic β-cells secrete inadequate insulin in response to elevated glucose. A known culprit in metabolic diseases is excessive exposure to glucocorticoids (GCs). GCs increase hepatic gluconeogenesis, decrease insulin sensitivity in skeletal muscle and adipose tissue and suppress the development of β-cells. In rodents, inactive GC 11-dehydrocorticosterone (A) is converted to active corticosterone (B) by the enzyme 11β-hydroxyster...

ea0013oc1 | Steroid synthesis and action | SFEBES2007

Monogenic polycystic ovary syndrome (PCOS) due to novel mutations in the H6PD gene - apparent cortisone reductase deficiency (ACRD)

Slabbert Ana , Lavery Gareth , Connell John , Walker Elizabeth , Stewart Paul

ACRD presents with clinical features of hyperandrogenism in females similar to those of PCOS (acne, hirsutism, oligomenorrhea, infertility), and precocious puberty in males. Obesity also occurs in some cases. Increased cortisol clearance leads to an increased hypothalamic-pituitary-adrenal axis drive resulting in elevated serum androgen levels and a decreased urinary cortisol metabolite: cortisone metabolite ratio below 0.5 (normal adult range 0.7–1.3). These observations...

ea0013p160 | Diabetes, metabolism and cardiovascular | SFEBES2007

Immunohistochemical localisation of 11β-hydroxysteroid dehydrogenase type 1 in murine pancreatic islets

Swali Angie , Walker Elizabeth , Tomlinson Jeremy , Stewart Paul

The metabolic syndrome, which encompasses features of obesity, insulin resistance, dyslipidaemia and hypertension, has been associated with excessive glucocorticoid (GC) exposure. The pancreas is a target of the adverse affects of GC action, resulting in β-cell damage and reduced glucose-stimulated insulin secretion (GSIS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the in vivo conversion of inactive to active glucocorticoids (cortisone E/11-de...

ea0028p302 | Steroids | SFEBES2012

Reversal of age-induced dermal atrophy in 11β-hydroxysteroid dehydrogenase type 1-null mice

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

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

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...

ea0015p150 | Diabetes, metabolism and cardiovascular | SFEBES2008

Activation of the unfolded protein response pathway in the skeletal muscle of hexose-6-phosphate dehydrogenase knockout mice induces a severe myopathy

Lavery Gareth , Bujalska Iwona , Turan Nil , Falciani Francesco , Walker Elizabeth , Stewart Paul

Hexose-6-phosphate dehydrogenase (H6PD) is a sarcoplasmic reticulum (SR) resident enzyme that metabolizes glucose-6-phosphate and generates NADPH that drives the activation of glucocorticoids by 11β-hydroxysteorid dehydrogenase type 1. H6PD KO mice exhibit improved skeletal muscle insulin sensitivity increased glucose uptake and glycogen storage. However, H6PD KO mice also develop a myopathy with switching from Type II to Type I fibers. Affected muscles have apparently no...