Endocrine Abstracts

Several enzymes are expressed in adipose tissue which catalyse interconversion of steroids, generating oestrogens (aromatase), androgens (5α-reductase 1), and glucocorticoids (11β-HSD1). These steroids may activate local receptors which influence body fat accumulation and distribution, or be secreted to exert endocrine effects. Several mouse models (e.g. aromatase and 11β-HSD1 knockout mice and studies with 11β-HSD1 inhibitors) illustrate the potential impo...

Fatty liver disease is strongly associated with insulin resistance. In order to elucidate the causality of this complex relationship, we studied insulin resistance in a rodent model of fatty liver disease – the choline deficient diet (CDD) – in which fatty liver occurs without generalised obesity. C57Bl/6 mice were fed a low fat (10% calories as fat, ‘Lo’) or isocaloric high fat diet (45% calories as fat, ‘Hi’) for 3 weeks; then half of the animal...

Objective:The activity of hepatic enzymes that metabolise glucocorticoids is altered in the setting of the metabolic syndrome. Westerbacka et al suggested a specific association between fatty liver and increased 5beta-reductase enzyme activity (J Clin Endocrinol Metab 2003). We hypothesised that non-alcoholic fatty liver disease (NAFLD), which is strongly associated with insulin resistance, may be primarily responsible for these changes.<p cla...

Recent investigations have suggested that 11ß-hydroxysteroid dehydrogenase-1 (11ßHSD1) activity influences development of atherosclerotic lesions and that pharmacological inhibition of this enzyme may have therapeutic benefits. Whilst these findings have been attributed to glucocorticoid metabolism, 11ßHSD1 also inter-converts 7-oxysterols (oxidized products of cholesterol which may promote atherogenesis). This study investigates whether metabolism of 7-oxystero...

Obesity is associated with decreased hepatic reactivation of glucocorticoids (Gc) by 11β-hydroxysteroid dehydrogenase type 1 (11HSD) and increased metabolism of glucocorticoids by hepatic A-ring reductases, which may contribute to activation of the hypothalamic-pituitary-adrenal axis. Androgen action encourages central obesity and increased metabolic complications, possibly by altering Gc metabolism.This study investigates the role of gonadal androg...

The Metabolic Syndrome (insulin resistance, hyperglycaemia, dyslipidaemia, hypertension) amplified by visceral obesity resembles Cushing's but plasma cortisol levels are not usually elevated. To explain this paradox altered tissue sensitivity to glucocorticoids has been invoked. 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) reactivates cortisone to cortisol, thus amplifying local glucocorticoid action. An adipose-selective increase in 11b-HSD1 may underlie the Metabolic S...

Objective: High dose growth hormone (rhGH) regimens (2 to 4 mg/day) have been shown to increase circulating insulin-like growth factor (IGF)-I to supra-physiological levels in human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (CART). This setting may improve immunologic output. However, a high plasma IGF-I concentration has detrimental effects on glucose metabolism, which hampers the use of high dose rhGH regimens.Me...

The metabolism of glucocorticoids within adipose tissue, by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), is known to be altered in obesity and following high fat feeding. Until recently, little attention has been paid to the fat depots found directly adjacent to blood vessels. Emerging evidence suggests that perivascular adipose may play a key role in modulating vascular function. The presence of steroidogenic enzymes within perivascular adipose, and the eff...

Bile acids inhibit glucocorticoid and mineralocorticoid metabolism. However bile acids may also influence hormone action by modulating steroidogenesis in the adrenal gland. In rodents adrenal cholesterol supply for steroidogenesis is derived from circulating HDL through the actions of scavenger receptor SR-B1. Since hepatic SR-B1 expression is known to be regulated by bile acids, we have investigated whether adrenal SR-B1 is similarly affected and, if so, whether adrenal lipid...

Mifepristone (RU38486) is a progesterone and glucocorticoid receptor antagonist which is used clinically to induce medical abortion, and as a research tool, e.g., in metabolic syndrome and depression. We aimed to develop a sensitive method to detect and quantify mifepristone in human plasma.Analyses were developed using a Surveyor HPLC system, with a mobile phase of methanol:ammonium acetate (5 mM) (70:30; 0.4 ml/min) and a C18 column (5 μm; 2.1&#21...