Endocrine Abstracts

In Cushing's Syndrome, elevated circulating cortisol levels are responsible for the association of central obesity, hypertension, insulin resistance, hyperglycaemia, and dyslipidaemia. Recent evidence suggests that there are subtle elevations in circulating cortisol concentrations amongst patients with hypertension and insulin resistance, and these are predicted by low birthweight suggesting that they may be programmed by events occurring in early life. In addition, there is e...

The hypothalamic-pituitary adrenal (HPA) axis plays a key role in the metabolic response to stress, so it is to be anticipated that cortisol signalling might in turn be regulated by nutritional status. This regulation might operate either centrally, controlling ACTH and hence plasma cortisol, or peripherally, controlling metabolism of cortisol in target tissues.Plasma cortisol levels are elevated during starvation in animals and a recent meta-analysis co...

Similarities between the metabolic syndrome and Cushing’s syndrome, and reversibility of the features of Cushing’s syndrome, suggest that cortisol may contribute to pathophysiology in both conditions and that reducing cortisol action may provide a novel therapeutic approach in metabolic syndrome. There is substantial evidence that circulating cortisol concentrations are higher in people with hypertension and glucose intolerance. The basis for t...

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...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisone (E) to cortisol (F) within the endoplasmic reticulum (ER) of adipocytes and hepatocytes. In its purified state 11beta-HSD1 is principally a dehydrogenase, converting F to E. Oxo-reductase activity can be regained by the addition of an NADPH regeneration system. In vivo hexose-6-phosphate ...

Endokinin B (EKB) is a recently identified tachykinin whose role is not yet fully understood. EKB displays equivalent affinity for the three tachykinin receptors as substance P (SP) which it is often found co-expressed with. SP has been implicated in a variety of neuroendocrinological responses including stress regulation, and affective and anxiety-related behaviours. An important aspect, therefore, is to dissect a distinct role for EKB from that of SP. Here, we have attempted...

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...

In order to assess the frequency and timing of recurrence in a group of patients with Graves’ disease and the predictors of recurrence, 197 patients were sampled, who were first seen in the OCDEM clinic in either 2001 or 2002 and put on anti-thyroid medication. Graves’ disease was diagnosed by the presence of low TSH levels ± symmetrical goitre ± uniform radioactive iodine uptake ± eye disease ± high levels of thyroid hormones. Patients with <...

Methyl oxime–trimethylsilyl (MO-TMS) derivatisation with gas chromatography–mass spectrometric (GC-MS) analysis has been well established in the analysis of glucocorticoids and is still used in many laboratories for profiling endogenous steroids for clinical purposes. There appears to be a clinical need to extend the analysis to xenobiotic glucocorticoids, primarily to elucidate cases of patients presenting with adverse symptoms associated with glucocorticoid excess,...