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Society for Endocrinology BES 2017

Harrogate, UK
06 Nov 2017 - 08 Nov 2017

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SfE BES 2017 will be on the 6-8 November 2016 in Harrogate, UK.

Oral Communications

Adrenal and Steroids

ea0050oc4.1 | Adrenal and Steroids | SFEBES2017

Predicted benign and silent SNPs in CYP11A1 cause primary adrenal insufficiency through missplicing

Maharaj Avinaash , Buonocore Federica , Meimaridou Eirini , Ruiz-Babot Gerard , Guasti Leonardo , Peng Hwei-Ming , Capper Cameron , Prasad Rathi , Crowne Elizabeth , Cheetham Timothy , Brain Caroline , Suntharalingham Jenifer , Striglioni Niccolo , Yuksel Bilgin , Gurbuz Fatih , Auchus Richard , Spoudeas Helen , Guran Tulay , Johnson Stephanie , Fowler Dallas , Duncan Emma , Conwell Louise , Drui Delphine , Cariou Bertrand , Siguero Juan Pedro Lopez , Harris Mark , Donaldson Malcolm , Achermann John , Metherell Lou

Background: CYP11A1 encodes the P450 side chain cleavage enzyme (P450scc) responsible for initiating steroidogenesis and classically gives rise to disordered sex development plus adrenal and gonadal insufficiency. The rs6161 variant in exon 5 of CYP11A1 (c.940G>A; p.E314K) has previously been considered as ‘benign’. When next generation sequencing was performed in patients with primary adrenal insufficiency of unknown etiology the rs6161 variant was foun...

ea0050oc4.2 | Adrenal and Steroids | SFEBES2017

Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional pathway involving HDAC6

Kershaw Stephen , Morgan David , Boyd James , Spiller David , Iqbal Mudassar , Zindy Egor , Brass Andy , Matthews Laura , Ray David

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. The inactive GR is held in the cytoplasm in a multi-protein complex, which upon ligand binding undergoes a conformational change. Activated GR translocates to the nucleus to regulate gene expression (over hours), but some effects occur more rapidly. Gc inhibit cell migration through an uncertain mechanism. We now show a very rapid effect, and surprising...

ea0050oc4.3 | Adrenal and Steroids | SFEBES2017

Local reactivation of glucocorticoids by 11β-HSD1 mediates their detrimental effects on bone

Fenton Chloe , Doig Craig , Raza Karim , Cooper Mark , Lavery Gareth , Hardy Rowan

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

ea0050oc4.4 | Adrenal and Steroids | SFEBES2017

The role of “stress” in aldosterone-mediated hypertension: circumstantial evidence from the “stress subtraction” experiment of adrenal vein sampling

Kline Gregory , Darras Pol , Leung Alexander , Chin Alex , So Benny , Holmes Daniel

Background: Primary aldosteronism (PA) accounts for a significant proportion of patients with hypertension. There has been a focus on ACTH in the pathogenesis of aldosterone secretion even with suppressed renin. With the link between psychological stress and cardiovascular disease as well as the association between anxiety and PA, there may be broader neurohormonal “stress” stimuli that modulate aldosterone production in PA patients, beyond the HPA axis. PA patients ...

ea0050oc4.5 | Adrenal and Steroids | SFEBES2017

NAD+ availability modulates 11β-HSD1 mediated glucocorticoid regeneration in mouse skeletal muscle

Elhassan Yasir , Fletcher Rachel , Cartwright David , Oakey Lucy , Garten Antje , Doig Craig , Lavery Gareth

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an NADPH-dependant oxo-reductase located in the sarcoplasmic reticulum (SR) lumen of skeletal muscle. It generates active glucocorticoids to regulate permissive and adaptive metabolism. Hexose-6-phosphate dehydrogenase (H6PD) interacts with 11β-HSD1 to generate an appropriate NADPH/NADP+ ratio to support activity. H6PD depletion impairs SR NADPH generation triggering 11β-HSD1 to assume glucocorticoid ina...

ea0050oc4.6 | Adrenal and Steroids | SFEBES2017

Distinct patterns of glucocorticoid metabolism in patients with HNF1A-MODY have the potential to confer a beneficial metabolic phenotype

Juszczak Agata , Gilligan Lorna C. , Hughes Beverly A. , Hassan-Smith Zaki K. , Arlt Wiebke , McCarthy Mark I. , Tomlinson Jeremy W. , Owen Katharine R.

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...