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Tissue-specific dysregulation of cortisol metabolism in equine laminitis.
Abstract: The role of glucocorticoids (GCs) in the pathogenesis of laminitis is incompletely understood. Local tissue activity of GC is regulated by the steroid converting enzyme, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1). Changes in integumentary (skin and hoof lamellar) 11beta-HSD activity occurring during laminitis could affect the extent to which GCs are involved in its development. Objective: That changes in integumentary 11beta-HSD-1 activity associated with the laminitic condition would lead to elevated local tissue levels of GCs, which could subsequently contribute, through paracrine and autocrine mechanisms, to the further development of laminitis; and that similar changes in 11beta-HSD-1 activity would be evident in both skin and hoof lamellar tissue. Methods: Activity of 11beta-HSD-1 was determined in skin and hoof lamellar tissue specimens obtained from normal and laminitic horses using a radiometric assay. Skin samples were obtained from 10 normal horses and from 10 horses before and after induction of acute laminitis following administration of starch via nasogastric tube. Hoof lamellar samples were obtained from 10 normal horses, 10 horses following induction of acute laminitis and 4 chronically-foundered horses. Bidirectional 11beta-HSD-1 activity was measured in both skin and lamellar tissues. Results: 11-ketoreductase activity exceeded 11beta-dehydrogenase activity in both skin and lamellar tissues. Cutaneous activity was higher than lamellar 11beta-HSD-1 activity in all groups. Both ketoreductase and dehydrogenase activity increased in skin and lamellae following experimental induction of acute laminitis, but the increase in ketoreductase activity was substantially greater than that for dehydrogenase in the lamellae. Induction of acute laminitis was attended by increases of 227 and 220% in cutaneous dehydrogenase and ketoreductase activity, respectively, and 173 and 398% in lamellar dehydrogenase and ketoreductase activity, respectively (P<0.05). Conclusions: The 11-ketoreductase moiety of 11beta-HSD-1 plays a role in equine skin and hoof lamellae regarding the regulation of local glucocorticoid activity. Increased 11-ketoreductase activity will lead to increased local tissue GC activity by virtue of conversion of cortisone to cortisol. Conclusions: The laminitic condition is attended by integumentary biochemical changes that enhance the local concentration of cortisol, especially in the hoof lamellar interface. Through multiple and diverse actions, increased local GC activity contributes to the pathogenesis and morbidity associated with laminitis. Pharmacological manipulation of 11beta-HSD-1 deserves further investigation regarding the prevention and treatment of laminitis.
Publication Date: 2004-02-06 PubMed ID: 14756370DOI: 10.2746/0425164044864750Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the role of glucocorticoids (GCs) in causing equine laminitis, a crippling hoof disease in horses. Changes in the activity of a steroid converting enzyme in the skin and hooves of horses might influence how much GCs contribute to laminitis.
Research Objective
The researchers hypothesized that changes in the activity of the steroid converting enzyme, specifically, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1), would result in increased levels of GCs, which could contribute to laminitis development. They anticipated that these changes would be observed in both the skin and hoof lamellar tissue.
Research Methods
- The researchers tested this hypothesis by determining the activity of the 11beta-HSD-1 enzyme in skin and hoof lamellar tissue from both normal and laminitic horses.
- The sampling included 10 normal horses, 10 horses before and after the induction of acute laminitis using starch administration, and 4 chronic laminitis patients.
- An important part of the process was the measurement of both the 11-ketoreductase and dehydrogenase activity, components of the 11beta-HSD-1 enzyme, in skin and lamellar tissues.
Research Findings
- The research findings showed that the 11-ketoreductase activity in both skin and lamellar tissues exceeded the dehydrogenase activity, and that the skin activity was higher in all groups.
- Both ketoreductase and dehydrogenase activity increased in skin and lamellar tissues following the experimental induction of acute laminitis. The increase in ketoreductase activity was significantly greater than that of dehydrogenase, especially in the lamellar tissue.
- Increases of 227% and 220% were observed in cutaneous dehydrogenase and ketoreductase activity, respectively, and increases of 173% and 398% were seen in lamellar dehydrogenase and ketoreductase activity, respectively after inducing acute laminitis.
Research Conclusions
- This study indicates that the 11-ketoreductase part of the 11beta-HSD-1 enzyme plays a crucial role in managing local GC activity in equine skin and hoof lamellae.
- The results also show that an increase in 11-ketoreductase activity leads to a boost in local tissue GC activity by converting cortisone to cortisol.
- The authors conclude that horses suffering from laminitis experience biochemical changes that increase the local concentration of cortisol, particularly in the hoof lamellar interface. This increase in local GC activity contributes to the development and severity of laminitis.
- The use of pharmaceutical interventions to manipulate 11beta-HSD-1 deserves further exploration, as it could potentially help in preventing and treating laminitis.
Cite This Article
APA
Johnson PJ, Ganjam VK, Slight SH, Kreeger JM, Messer NT.
(2004).
Tissue-specific dysregulation of cortisol metabolism in equine laminitis.
Equine Vet J, 36(1), 41-45.
https://doi.org/10.2746/0425164044864750 Publication
Researcher Affiliations
- Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri at Columbia, Missouri 65211, USA.
MeSH Terms
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
- Acute Disease
- Animals
- Chronic Disease
- Female
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Glucocorticoids / metabolism
- Hoof and Claw
- Horse Diseases / metabolism
- Horses
- Hydrocortisone / metabolism
- Inflammation / metabolism
- Inflammation / veterinary
- Lameness, Animal / etiology
- Lameness, Animal / metabolism
- Male
- Skin / enzymology
Citations
This article has been cited 4 times.- Morgan R, Keen J, Halligan D, O'Callaghan A, Andrew R, Livingstone D, Abernethie A, Maltese G, Walker B, Hadoke P. Species-specific regulation of angiogenesis by glucocorticoids reveals contrasting effects on inflammatory and angiogenic pathways. PLoS One 2018;13(2):e0192746.
- Morgan RA, Keen JA, Walker BR, Hadoke PW. Vascular Dysfunction in Horses with Endocrinopathic Laminitis. PLoS One 2016;11(9):e0163815.
- Steelman SM, Chowdhary BP. Plasma proteomics shows an elevation of the anti-inflammatory protein APOA-IV in chronic equine laminitis. BMC Vet Res 2012 Sep 27;8:179.
- Johnson PJ, Wiedmeyer CE, Messer NT, Ganjam VK. Medical implications of obesity in horses--lessons for human obesity. J Diabetes Sci Technol 2009 Jan;3(1):163-74.
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