Endocrine Abstracts

Background: Vascular impairment, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in humans with obesity, insulin resistance or Cushing’s syndrome. Similar endocrine disorders in horses, resulting in insulin resistance, are associated with laminitis, a dysfunction of the vasculature supplying the hooves, the mechanism of which is unclear. We hypothesised that horses with insulin resistance have both local and systemic evidence of vascul...

Activation of the hypothalamic–pituitary–adrenal (HPA) axis and altered tissue glucocorticoid action in obesity and metabolic syndrome has been attributed to altered peripheral cortisol metabolism. In human obesity, cortisol clearance is increased with up-regulation of A-ring reductases and down-regulation of cortisol-regenerating 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver, while in adipose tissue 11β-HSD1 is up-regulated. Rodent studi...

Obesity is associated with metabolic and vascular dysfunction. Many models have shown insulin resistance reduces endothelium-dependent vasodilation but this is also seen in obese subjects with normal glucose tolerance. There is also evidence of increased response to vascular injury in obese animals, although the mechanisms underpinning this are not fully understood. This study used a mouse model of diet-induced obesity (DIO) to address the hypothesis that obesity causes metabo...

Although obesity affects men and women, the risks of associated metabolic disturbances (e.g. type 2 diabetes) differ between the sexes. Altered peripheral glucocorticoid metabolism may underpin the metabolic consequences of obesity; however, most research exploring this has focused on male animals. This study used a mouse model to investigate the hypothesis that alterations in glucocorticoid metabolism caused by diet-induced obesity (DIO) will be more profound in males than in...

Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disorder characterised by the gradual build-up of plaques in the arterial wall. Unstable plaques are more dangerous than stable plaques as they are prone to rupture and obstruct blood flow, resulting in heart attacks and strokes. Lipids play a key role in plaque progression, yet their exact involvement remains elusive. We hypothesise that stable or unstable plaques will have distinct spatial lipid phenoty...

Background: The 5α-reduced glucocorticoid, 5α-tetrahydrocorticosterone (5α-THB), displays a dissociated steroid profile exhibiting anti-inflammatory effects in a murine model of thioglycollate-induced peritonitis but failing to induce adverse metabolic effects caused by corticosterone. We assessed the topical anti-inflammatory properties of 5α-THB in a model of irritant dermatitis. Given the adverse effects of steroids on cutaneous wound healing, we also in...

Background: The effects of glucocorticoids (GC) on the developing zebrafish embryo (Zfe) are poorly characterised. We have assessed the effects of pharmacological and genetic manipulation of cortisol and glucocorticoid receptors (GR) on global development and stress response during the first 120 hpf.Methods: Cortisol production was modulated by inhibiting the enzyme 11b hydroxylase using morpholino gene knockdown (MO) or incubation in the drug metyrapone...

Chronic inflammatory disease is often accompanied by angiogenesis and fibrosis. Glucocorticoids (GCs) exert anti-inflammatory and anti-angiogenic effects, in which macrophages are a major target. Local endogenous GC action is controlled by 11β-hydroxysteroid dehydrogenase (11β-HSD), with the type 1 isozyme, 11β-HSD1 converting inactive GCs into active forms. Mice deficient in 11β-HSD1 have a phenotype consistent with reduced glucocorticoid action, including...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone into active cortisol. We have previously shown attenuated atherosclerosis development, reduced plasma monocyte chemoattractant protein-1 (MCP-1) and reduced macrophage/T cell infiltration within atherosclerotic lesions in 11β-HSD1−/−×ApoE−/− double knock-out (DKO) mice fed western diet (WD)....

High plasma levels of glucocorticoids cause metabolic disease (central obesity, hypertension, diabetes) and increase risk of cardiovascular disease. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents). Recent work has shown the pathological importance of elevated adipose tissue 11β-HSD1 expression in develo...