Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2013

Oral Communications

Young Endocrinologists prize session

ea0031oc1.1 | Young Endocrinologists prize session | SFEBES2013

TNFα directly regulates in vivo corticosteroid metabolism in inflammatory arthritis

Nanus Dominika E , Filer Andrew , Fisher Benjamin A , Taylor Peter C , Stewart Paul , Buckley Christopher D , McInnes Iain , Cooper Mark S , Raza Karim

Within the synovium of patients with rheumatoid arthritis (RA), synovial fibroblasts generate active corticosteroids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In vitro, this enzyme is strongly up-regulated by pro-inflammatory cytokines such as tumour necrosis factor α (TNFα) and IL1β. In this study, we determined the relationship between inflammation and global 11β-HSD1 activity in vivo, in a clini...

ea0031oc1.2 | Young Endocrinologists prize session | SFEBES2013

Macrophage-specific 11β-hydroxysteroid dehydrogenase type 1 deficiency promotes angiogenesis but impairs resolution of K/BxN serum induced arthritis

Zhang Zhenguang , Coutinho Agnes , Hadoke Patrick , Salter Donald , Seckl Jonathan , Chapman Karen

Chronic inflammatory disease is often accompanied by angiogenesis and fibrosis. Glucocorticoids (GCs) exert anti-inflammatory and anti-angiogenic effects, in which macrophages are a major target. Local endogenous GC action is controlled by 11β-hydroxysteroid dehydrogenase (11β-HSD), with the type 1 isozyme, 11β-HSD1 converting inactive GCs into active forms. Mice deficient in 11β-HSD1 have a phenotype consistent with reduced glucocorticoid action, including...

ea0031oc1.3 | Young Endocrinologists prize session | SFEBES2013

11β-HSD1KO mice are protected from glucocorticoid dependent age-associated muscle atrophy

Hassan-Smith Zaki , Morgan Stuart , Bujalska Iwona , Abrahams Lianne , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoids (GCs) are prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including a decline in muscle mass and function which has similarities to age related sacropaenia. Within skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) amplifying local GC action. We hypothesise that 11β-HSD1 mediated intramyoce...

ea0031oc1.4 | Young Endocrinologists prize session | SFEBES2013

A serum microRNA profile potentially associated with glucocorticoid mediated insulin resistance

Gathercole Laura , Doig Craig , Hazlehurst Jonathan , Borrows Sarah , Stewart Paul , Lavery Gareth , Tomlinson Jeremy

Patients with glucocorticoid (GC) excess develop insulin resistance and central obesity. We have demonstrated that GCs have tissue-specific effects on insulin sensitivity in humans, causing resistance in skeletal muscle but sensitivity in subcutaneous adipose tissue. The molecular mechanisms that underpin these differences remain poorly understood. Over the last decade small non-coding RNAs (microRNAs–miRNAs) controlling protein expression have been identified, representi...

ea0031oc1.5 | Young Endocrinologists prize session | SFEBES2013

Inhibition of 5α-reductase type 1 with dutasteride impairs insulin sensitivity

Upreti Rita , Hughes Katherine , Gray Calum , Minns Fiona , Marshall Ian , Stewart Laurence , Walker Brian , Andrew Ruth

5α-Reductase (5αR) inhibitors decrease prostatic dihydrotestosterone in benign prostatic hyperplasia (BPH) treatment; finasteride inhibits 5αR type 2, while dutasteride inhibits 5αR1 and 2. 5αRs, especially 5αR1, are also expressed in metabolic tissues regulating actions of androgens and other substrates, including glucocorticoids.Hypothesis: 5αR1 inhibition with dutasteride induces metabolic dyshomeostasis.<p class...

ea0031oc1.6 | Young Endocrinologists prize session | SFEBES2013

Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle

Sinha Akash , Hollingsworth Kieren , Ball Steve , Cheetham Tim

Objective: Suboptimal mitochondrial function has been implicated in several disorders where fatigue is a prominent feature. Vitamin D deficiency is a well-recognised cause of fatigue and myopathy. The aim of this study was to examine the effects of cholecalciferol therapy on skeletal mitochondrial oxidative function in symptomatic, vitamin D deficient individuals.Design: This longitudinal study assessed mitochondrial oxidative phosphorylation in the gast...

ea0031oc1.7 | Young Endocrinologists prize session | SFEBES2013

Autosomal dominant hypocalcemia type 2 is caused by germline GNA11 gain-of-function mutations

Howles Sarah , Nesbit Andrew , Hannan Fadil , Babinsky Valerie , Head Rosie , Cranston Treena , Rust Nigel , Thakker Rajesh

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and gain-of-function mutations in autosomal dominant hypocalcemia (ADH). Recently, loss-of-function Gα11 mutations have been identified to cause FHH2 and we hypothesised that gain-of-function Gα11...

ea0031oc1.8 | Young Endocrinologists prize session | SFEBES2013

Kisspeptin advances ovulation in healthy women

Comninos Alexander , Jayasena Channa , Nijher Monica , Abbara Ali , De Silva Akila , Veldhuis Johannes , Ratnasabapathy Risheka , Izzi-Engbeaya Chioma , Lim Adrian , Patel Daksha , Ghatei Mohammad , Bloom Steve , Dhillo Waljit

Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to profound tachyphylaxis in women with hypothalamic amenorrhoea. It is not known whether exogenous kisspeptin can alter the m...