Searchable abstracts of presentations at key conferences in endocrinology

ea0031p141 | Growth and development | SFEBES2013

Impaired heart function and cardiac maturation in fetal mice with disrupted GR signalling in vascular smooth muscle and cardiomyocytes

Rog-Zielinska Eva A , Thompson Adrian , Moran Carmel , Kenyon Christopher J , Holmes Megan C , Chapman Karen E

Glucocorticoid signalling is essential for cardiac maturation late gestation. In mice, global glucocorticoid receptor deficiency (GR−/−) severely impairs cardiac function and ultrastructure at embryonic day (E) 17.5. To dissect direct effects of GR deficiency in the heart from effects on other systems, Sm22α-Cre mice were crossed with ‘floxed’ GR mice to generate SMGRKO mice with disrupted GR signalling in cardiomyocytes and vascular smoot...

ea0031p181 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

The role of hepatic 11β-hydroxysteroid dehydrogenase type 1 in cholesterol homeostasis

Manwani Kajal , Man Tak Y , Kenyon Christopher J , Andrew Ruth , Chapman Karen E , Seckl Jonathan R

11β-Hydroxysteroid dehydrogenase type one (11β-HSD1) converts inert glucocorticoids to active forms, amplifying intracellular glucocorticoid action. 11β-HSD1 also catalyses the reduction of seven-ketocholesterol (7KC) to 7β-hydroxycholesterol (7βHC). 7KC may inhibit cholesterol biosynthesis (Brown et al. 2002). Alteration of cholesterol homeostasis is a major atherosclerotic risk factor. 11β-HSD1 deficiency/inhibition is atheroprotective ...

ea0031p317 | Steroids | SFEBES2013

Molecular mechanisms underlying the anti-inflammatory properties of 5α-tetrahydrocorticosterone

Gastaldello Annalisa , Nixon Mark , Yang Chenjing , Saunders Philippa T K , Chapman Karen E , Walker Brian R , Andrew Ruth

Glucocorticoids (GCs) are highly effective anti-inflammatory drugs, however their use is limited by serious side effects. We have previously shown that 5αTHB binds GC receptor (GR) and suppresses inflammation in vitro and in vivo, without affecting metabolism. Here the underlying molecular mechanisms were explored in cell models of ligand-induced GR phosphorylation, nuclear localisation and gene transcription. Data are mean±S.E.M. (th...

ea0065op1.2 | Adrenal and Cardiovascular | SFEBES2019

Glucocorticoids promote mitochondrial fatty acid oxidation in the fetal heart

Urquijo Helena , Panting Emma N , Carter Roderick N , Agnew Emma J , Wyrwoll Caitlin S , Morton Nicholas M , Chapman Karen E , Ivy Jessica R

Background: The late gestational surge in glucocorticoids is vital for the maturation of fetal organs in preparation for birth and survival during the neonatal period. Metabolic maturation of cardiomyocytes involves a switch in fuel substrate from glucose utilization to fatty acid (FA) oxidation. In fetal cardiomyocytes, glucocorticoids induce expression of Ppargc1a (encoding PGC1a, a master regulator of mitochondrial capacity). We hypothesized that glucocorticoids pr...

ea0038p365 | Reproduction | SFEBES2015

Investigation into the effects of glucocorticoids in a mouse model of induced menstruation

Murray Alison A , Armstrong Gregory M , Murgai Reena , Gray-Renfrew Alexandra E , Vere Rebecca E A , Chapman Karen E , Critchley Hilary O D

Introduction: Heavy menstrual bleeding (HMB) affects over 1 million women in the UK. At menses, progesterone (P4) withdrawal drives inflammation, tissue break-down and repair of the endometrium. Glucocorticoids are mediators of inflammation and angiogenesis. Our previous studies have demonstrated that differential endometrial expression of the glucocorticoid-metabolising enzymes, 11β-HSD-1 and -2, may play a role in HMB. We hypothesise that aberrant lo...

ea0025oc1.5 | Young Endocrinologists prize session | SFEBES2011

Atheroprotection by 11β-HSD1 deficiency in ApoE−/− mice: role of both glucocorticoid and 7-oxysterol factors

Mitic Tijana , Hadoke Patrick W F , Chuaiphichai Surawee , Man Taq Y , Miller Eileen , Andrew Ruth , Walker Brian R , Chapman Karen E , Seckl Jonathan R

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...

ea0019oc9 | Neuroendocrine and Steroids | SFEBES2009

11β-hydroxysteroid dehydrogenase type 1 activity limits fibrosis following bleomycin lung injury by augmenting active glucocorticoids

Yang Fu , Duffin Rodger , Brownstein David G , Coutinho Agnes , Rossi Adriano G , Savill John S , Seckl Jonathan R , Chapman Karen E

Glucocorticoids are potent anti-inflammatory agents. Endogenous glucocorticoid action is modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) which interconverts active (cortisol, corticosterone) and intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 regenerates active glucocorticoids. 11β-HSD 1 highly expressed in the lung but its role is little explored.Immunohistochemical staining of mouse ...

ea0056gp58 | Bone and Osteoporosis | ECE2018

Investigating glucocorticoids as mediators of increased bone marrow adiposity during caloric restriction

Lovdel Andrea , Suchacki Karla , Sulston Richard J , Wallace Robert J , Macpherson Gavin , Stimson Roland H , Homer Natalie ZM , Chapman Karen E , Cawthorn William P

Background: Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass in healthy humans and further increases in diverse clinical conditions, including obesity/diabetes, osteoporosis and following caloric restriction (CR). However, why BMAT increases during CR remains unknown. One possibility is that this is mediated by glucocorticoid (GC) excess. GC action on target tissues depends on circulating and intracellular concentrations of t...