Endocrine Abstracts

Background: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations.Objective: To describe the clinical manifestations of subjects with SDH-B gene mutations.Design: Retrospective case series.Patients: Thirty-two subjects with SDH-B gene mutations followed-up between 1975 and 2007. Mean follow-up of 5.8 years (S.D....

We have previously shown that the orexigenic and peripheral adipogenic effects of ghrelin are mediated by its effect on the metabolic enzyme AMPK. As the cannabinoid (CB1)-antagonist rimonabant inhibits the orexigenic effect of ghrelin, we suggest that there is an interaction between cannabinoids and ghrelin.To study the involvement of CB1 in the effects of ghrelin, wild-type (WT) and CB1-knockout mice were treated with ghrelin and rimonabant.<p clas...

Cortisol is regenerated from cortisone by 11βHSD1 reductase in cells from VAT. Mice overexpressing 11βHSD1 in adipocytes have more glucocorticoids in the portal vein (PV) and hepatic insulin resistance. In humans, hepatic vein (HV) sampling during D4-cortisol tracer infusion confirmed substantial splanchnic cortisol generation, and indirect modelling suggested major contributions from both liver and VAT. PV sampling in dogs, however, did not reveal cortisol release f...

MIF is a potent pro-inflammatory mediator that opposes the anti-inflammatory actions of glucocorticoids (Gc) and is involved in the pathogenesis of multiple diseases. The MIF promoter is inhibited by Gc in lymphocytes (CEMC7A) but not in epithelial cells (A549), despite expression of functional glucocorticoid receptors (GR) in both. Deletion studies localized the cis element responsible for Gc inhibition to between MIF −71 and +85. This sequence contained no GR binding s...

Fetal glucocorticoid exposure is a key mechanism involved in adverse programming outcomes in the adult, including hypertension, anxiety and insulin resistance. While glucocorticoids may exert their effects directly on the fetus, they may also affect fetal growth through indirect effects on placental function. Regulation of fetal glucococorticoid exposure is achieved by the placental glucocorticoid barrier, which involves glucocorticoid inactivation within the labyrinth zone of...

Background: The identification of MRAP in 2005 as the first melanocortin-2-receptor (MC2R)/ACTH receptor accessory protein provided insight into the regulation of the melanocortin receptor system. Mutations in MRAP cause Familial glucocorticoid deficiency, an autosomal recessive disorder resulting in isolated cortisol deficiency. In vitro studies showed that MRAP was essential for the functional expression of the MC2R. The melanocortin receptor (MCR) family (MC1R to MC5...

Introduction: Testosterone (T) improves muscle strength in hypogondal men. It is unclear if testosterone has similar effects in prefrail and frail elderly men with low T. We conducted a randomised double-blind placebo-controlled parallel group study to determine the effects of T on muscle mass and strength, physical function and quality of life in prefrail and frail elderly men.Methods: Two hundred and sixty two prefrail and frail elderly men (Fried e...

High systemic cortisol levels contribute to insulin resistance and may exacerbate the development of diabetes by impairing the insulin secretory response of the pancreatic beta-cells (β-cells). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key modulator of glucocorticoid effect within target tissues and high adipose or liver levels of this enzyme may contribute to obesity and/or metabolic disease. We investigated cellular localization of 11β-HSD1 ...