Endocrine Abstracts

Large animals are increasingly used a models for endocrine research. Unlike rodents they are cortisol-dominant and thus more similar to humans. In this study we use two novel analytical methods to compare the steroid profile of pigs, sheep and humans; 1. Simultaneous quantification of primary glucocorticoids, glucocorticoid precursors and mineralocorticoids in plasma (>20 steroids); 2.Quantification of glucocorticoids metabolites (>10 ...

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...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose, and skeletal muscle. ABCC1 is a transmembrane ‘drug-resistance’ transporter expressed in adipose tissue and skeletal muscle with previously unknown physiological function. We recently showed that ABCC1 modulates intracellular GC concentrations and action in adipose. Here, we tested the hypothesis that Abcc1 regulates GC concentrations in skeletal mu...

Obesity and metabolic syndrome are highly prevalent in horses and ponies worldwide. Equine Metabolic Syndrome (EMS) shares much of the same pathophysiology with its human counterpart including adipose tissue dysfunction and insulin dysregulation. Vitamin D deficiency is strongly associated with obesity and insulin resistance in humans and supplementation is often recommended. In horses our understanding of vitamin D biology is limited and its association with EMS unknown. The ...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose and skeletal muscle. GC access to corticosteroid receptors in these tissues is regulated e.g. by pre-receptor metabolism. We recently identified a role for ABCC1, a transmembrane ‘drug-resistance’ transporter, as a GC exporter which limits intracellular GC concentrations and action in adipose tissue. Here, we tested the hypothesis that ABCC1, which i...

Glucocorticoids (GC) have potent anti-inflammatory effects, acting mainly through the glucocorticoid receptor (GR). However GCs have debilitating side effects and a safer alternative is required. 5α-tetrahydrocorticosterone (5αTHB, a metabolite of the natural rodent glucocorticoid corticosterone) may provide a solution: 5αTHB is anti-inflammatory in vivo, effective topically to suppress irritant dermatitis, but with fewer syst...

Glucocorticoids (GC) have potent anti-inflammatory effects, acting mainly through the glucocorticoid receptor (GR). However GCs have debilitating side effects and a safer alternative is required. 5α-tetrahydrocorticosterone (5αTHB, a metabolite of the natural rodent glucocorticoid corticosterone) may provide a solution: 5αTHB is anti-inflammatory in vivo, effective topically to suppress irritant dermatitis, but with fewer syst...

Cortisol conversion to 20β-dihydrocortisol (20β-DHF) has been reported in many tissues and cells, including skin, muscle, thrombocytes and fibroblasts, although the enzyme responsible is poorly characterised. We have attributed 20β-DHF generation to carbonyl reductase 1 and shown increased activity of this pathway in adipose tissue in obesity in humans, horses and mice. This study addressed the hypothesis that 20β-DHF activates gl...

Cortisol conversion to 20β-dihydrocortisol (20β-DHF) has been reported in many tissues and cells, including skin, muscle, thrombocytes and fibroblasts, although the enzyme responsible is poorly characterised. We have attributed 20β-DHF generation to carbonyl reductase 1 and shown increased activity of this pathway in adipose tissue in obesity in humans, horses and mice. This study addressed the hypothesis that 20β-DHF activates gl...