Endocrine Abstracts

Hypertension in obese Zucker rats is associated with raised plasma aldosterone, suppressed renin and increased hypothalamo–pituitary–adrenal activity. We investigated the possible causes and consequences of these associations by comparing adrenal gene expression and urinary electrolyte and steroid excretion patterns in lean and obese rats. Groups (n=11) of adult male lean and obese Zucker rats were held in metabolism cages for 7 days. Urine collected over the ...

Adult GH deficiency (AGHD) is a common sequela in patients with pituitary or brain tumors or in patients with a history of traumatic brain injury or cranial irradiation. In addition, approximately one third of children who were diagnosed with GH deficiency will remain GH deficient as adults. Since AGHD is characterized by diminished cardiovascular health, abnormal body composition, decreased muscle strength and aerobic capacity, poor quality of life, and increased mortality, i...

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...

Alterations in the rate of glucocorticoid(GC) metabolism induce compensatory changes in GC secretion under the control of the hypothalamic-pituitary-adrenal (HPA) axis. The principal routes of metabolic clearance of GCs are by hepatic A-ring reduction however the regulation of these enzymes is poorly understood. Recently we and others have demonstrated that bile acids act as potent inhibitors of GC metabolism by 5beta-reductase and 11beta-hydroxysteroid dehydrogenases in vi...

5alpha-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens. We previously demonstrated that transgenic disruption of 5aR1 predisposes male mice to fatty liver and insulin resistance when challenged with a high-fat diet. Here, we have dissected the contributions of androgens and glucocorticoids to the metabolic phenotype using 2 models of enzyme inhibition (trangenesis and pharmacology).Female 5aR1−/− mice (KO) and w...

Hepatic A-ring reduction of glucocorticoids is enhanced in obesity, perhaps contributing to compensatory activation of the hypothalamic-pituitary-adrenal axis and adrenal androgen excess. One pathway activated is the formation of tetrahydro metabolites by two sequential steps catalysed by 5beta-reductase (5bR) followed by 3alpha-hydroxysteroid dehydrogenases (3HSD). However, regulation of these enzymes is understood poorly. 5bR and 3HSD are also involved in the conversion of c...

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...

Background: 11β-hydroxysteroid dehydrogenases (11β-HSD1&2) interconvert cortisol (F) and cortisone (E). Although 11β-HSD1 reductase activity has been measured in vivo, E production (dehydrogenase activity) has not been quantified using a Gold Standard technique, steady state tracer infusion.Aim: To develop a method to measure E production in vivo using the stable isotope tracer d2-cortisone (d2E).Me...

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...

A 30-year-old woman with long standing type 1 diabetes presented with recurrent severe hypoglycaemia. One month earlier she had given birth to her first child. Before pregnancy her HbA1c had been 7.8 to 9.2 percent (RR 3.1 to 5.0 percent) but improved by the third trimester to 6.8 percent. Before pregnancy her total daily insulin dose was 50 units and by the third trimester it had only increased by 25 percent to 60 units. The pregnancy and birth were uneventful with no hypogly...