Projects per year
Abstract / Description of output
Equine Cushing's Disease (Pituitary pars intermedia dysfunction (PPID)) is a common condition of older horses but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterised by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 PPID horses compared with 15 healthy controls, we show that: in plasma, cortisol levels and cortisol binding to CBG were not different; in urine, glucocorticoid and androgen metabolites were increased up to four-fold; in liver, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression was reduced; in peri-renal adipose tissue 11β-HSD1 and carbonyl reductase 1 expression was increased; and tissue cortisol levels were not measurably different. The combination of normal plasma cortisol with markedly enhanced urinary cortisol metabolite excretion and dysregulated tissue-specific steroid-metabolising enzymes suggests that cortisol clearance is increased in PPID horses. We infer that the ACTH excess may be compensatory and pituitary pathology and autonomous secretion may be a secondary rather than primary pathology. It is possible, that successful therapy in PPID may be targeted either at lowering ACTH or, paradoxically, at reducing cortisol clearance.
Original language | English |
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Pages (from-to) | 3791–3800 |
Number of pages | 10 |
Journal | Endocrinology |
Volume | 159 |
Issue number | 11 |
Early online date | 4 Oct 2018 |
DOIs | |
Publication status | E-pub ahead of print - 4 Oct 2018 |
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Dive into the research topics of 'Dysregulation of cortisol metabolism in equine pituitary pars intermedia dysfunction'. Together they form a unique fingerprint.Projects
- 3 Finished
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Carbonyl Reductase 1 and 20¿¿-Dihydrocortisol: a novel glucocorticoid metabolism pathway in the pathogenesis of mineralcorticoid activation in obesity
Morgan, R.
1/09/17 → 1/03/22
Project: Research
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The role of corisol dysregulation in endocrinopathic laminitis: studentship ruth morgan
UK industry, commerce and public corporations
1/03/12 → 30/04/16
Project: Research
Profiles
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John Keen
- Royal (Dick) School of Veterinary Studies - Personal Chair of Equine Cardiovascular Medicine
Person: Academic: Research Active
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Mark Nixon
- Deanery of Clinical Sciences - Research Fellow
- Centre for Cardiovascular Science - Postdoctoral Researcher
Person: Academic: Research Active