Searchable abstracts of presentations at key conferences in endocrinology

ea0007p271 | Clinical case reports | BES2004

Normoprolactinaemic galactorrhoea in a male-to-female transsexual

Barber T , Basu A , Rizvi K , Chapman J

Hormonal therapies in the form of oestrogens, anti-androgens and progestogens are often used in the treatment of male-to-female transsexuals. We present the case of a 36 year old phenotypic male with karyotype 46XY who presented with normoprolactinaemic galactorrhoea likely to be related to prior oestrogen administration. He had been self-administering oestrogen and progesterone preparations continuously for 7 years (aged 26 - 33 years) in an attempt to develop female phenotyp...

ea0011p756 | Steroids | ECE2006

The glucocorticoid receptor 1a promoter in CD4+CD8+ thymocytes is rapidly upregulated following dexamethasone treatment in vitro

Nixon J , Sheridan J , Blackburn C , Chapman K

Glucocorticoid Receptor (GR) levels are increased in response to glucocorticoids (GC) in T-lymphoma cell lines susceptible to GC-induced cell death (GICD). The GR gene is transcribed from 5 promoters generating alternate first exons, 1A-1E, with 1A expression restricted to immune tissue and the cortex of the brain. Expression of the 1A-containing variant correlates with susceptibility to GICD in mouse thymocytes. Here we describe the time course of GC induction of total GR mRN...

ea0005oc12 | Cardiovascular Endocrinology | BES2003

Corticosteroid effects at the trafficking level on the pathway of key importance in blood pressure control

Hou J , Seckl J , Chapman K , Brown R

Regulation of the epithelial sodium channel (ENaC) trafficking in cells of the distal nephron is of major importance in the control of sodium reabsorption. Mutations in the genes compromising the molecular pathway by which corticosteroids regulate ENaC sodium reabsorption cause several hypertensive syndromes in humans. The molecular events underpinning ENaC exo- and endocytosis and the hormonal effects on ENaC trafficking are poorly understood. To start elucidating these pathw...

ea0005p227 | Steroids | BES2003

The 5' untranslated region of the rat glucocorticoid receptor contains elements important for cell-specfic promoter activity and glucocorticoid regulation

Munn H , Lyons V , McCormick J , Seckl J , Chapman K

Cellular sensitivity to circulating glucocorticoids is critical and is principally determined by the level of glucocorticoid receptor (GR). GR expression is most potently regulated by glucocorticoids themselves, although the mechanism is unknown. The rat GR gene encodes at least eleven alternate and untranslated exons 1, eight of which lie in a 3kb CpG island close to exon 2. We have recently shown that individual exons 1 are subject to tissue specific expression and regulatio...

ea0011p385 | Diabetes, metabolism and cardiovascular | ECE2006

Dietary regulation of peripheral glucocorticoid action: comparison of saturated and unsaturated fats

Man TY , Ramage L , Gokcel A , Michailidou Z , Kenyon CJ , Chapman K , Seckl JR , Morton NM

Obesity/Metabolic syndrome (insulin resistance, hypertension, cardiovascular disease) has reached epidemic levels in western societies. Aberrantly elevated glucocorticoid amplification by intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) within adipose tissue might explain the striking similarities between idiopathic obesity/metabolic syndrome and Cushing’s syndrome, causes by plasma GC excess. A major contributor to obesity/metabol...

ea0005oc21 | Obesity and Diabetes | BES2003

5alpha-Reduced glucocorticoid metabolites: Novel endogenous activators of glucocorticoid receptors(GR)

McInnes K , Livingstone D , Kenyon C , Chapman K , Walker B , Andrew R

Metabolism of glucocorticoids to dihydro and tetrahydro derivatives via hepatic 5alpha- and 5beta-reductases has been assumed to be a pathway of irreversible inactivation of glucocorticoids. However, 5alpha-reduced metabolites of other steroids (testosterone, aldosterone) have significant affinity for the parent hormone receptor. We have investigated whether 5alpha-reduced metabolites of corticosterone (B) are GR agonists.In hepatocytes from male lean Zucker rats (n=6) com...

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...