Endocrine Abstracts (2014) 34 P208 | DOI: 10.1530/endoabs.34.P208

Abnormal glucocorticoid metabolism in horses with metabolic syndrome

Ruth Morgan1,2, Patrick Hadoke1, Brian Walker1 & John Keen2

1The Queen’s Medical Research Institute, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; 2Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.

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 studies suggest this dysregulation is species-specific. This study addressed whether abnormalities of glucocorticoid metabolism occur in equine metabolic syndrome (EMS).

Morning (0900–1100 h) plasma cortisol and serum insulin concentrations were measured in 11 healthy controls and 12 EMS cases. Adipose (neck crest, peri-renal, and linea alba) and liver samples were obtained post-mortem and 11β-HSD1, 11β-HSD2, glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNA transcript levels quantified by qPCR. Cortisol metabolites were measured by GC–MS in urine aliquots from sub-groups (n=5–6) and corrected for creatinine concentration. Data are mean ± S.E.M.

Fasted serum insulin (P=0.002) but not plasma cortisol, was increased in EMS. Body condition score (/5) was higher in EMS (control 2.9±0.24 vs EMS 3.8±0.27, P=0.046) indicating obesity in this group. 11β-HSD1 mRNA was up-regulated in peri-renal (0.54±0.12 vs 1.25±0.29, P=0.011) and linea alba (0.57±0.16 vs 1.55±0.30, P=0.007) adipose, but not in neck crest adipose or liver, in EMS. No differences were detected in GR, MR or 11β-HSD2 mRNA levels. Urinary excretion of total cortisol metabolites was increased in EMS (P=0.041), with elevated α/β cortols, α/β cortolones, and 20α- and 20β-dihydrocortisol, but lower relative excretion of 5α-tetrahydrocortisol.

In conclusion, obese horses with metabolic syndrome, like humans, have increased cortisol clearance, and increased cortisol regeneration in adipose tissue by 11β-HSD1. The latter may provide a therapeutic target in equine metabolic syndrome. However, dysregulation of cortisol metabolism in equine liver is not mediated by altered 5α-reductase or 11β-HSD1, perhaps reflecting species-specific differences in regulation and/or alternative predominant pathways of glucocorticoid clearance in horses.

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