Domestic animal endocrinology2021; 76; 106620; doi: 10.1016/j.domaniend.2021.106620

Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy.

Abstract: Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.
Publication Date: 2021-02-18 PubMed ID: 33740552DOI: 10.1016/j.domaniend.2021.106620Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study focused on the effect of pergolide, a dopaminergic agonist, on horses with a common endocrine disorder called Pituitary pars intermedia dysfunction (PPID), specifically looking at muscle mass and regulation of skeletal muscle proteolysis. Despite the hypothesis that pergolide treatment could improve muscle atrophy and proteolysis markers, the results suggest the treatment may contribute to weight loss and improved insulin regulation in horses with PPID, but does not affect muscle mass or proteolysis markers.

Introduction to the Research

  • The research investigated the effects of an endocrine disorder in horses known as Pituitary pars intermedia dysfunction (PPID). This disorder frequently affects aged horses, with one of the symptoms being muscle atrophy, or the wasting away of muscle tissue.
  • Specifically, the researchers wanted to examine the correlation between muscle mass and the regulation of skeletal muscle proteolysis (the breakdown of proteins) in horses with PPID and muscle atrophy.
  • A significant part of the study involved analyzing the impact of a dopaminergic agonist known as pergolide on PPID horses. The initial hypothesis was that the muscle atrophy witnessed in PPID was a result of an increase in proteolysis, and that markers indicating this proteolysis and muscle atrophy would show improvement with pergolide treatment.

Methodology

  • For accurate comparisons, the researchers studied different markers such as muscle atrophy, adiposity (obesity), insulin regulation, skeletal muscle composition, and proteolysis in two groups of horses — those with PPID and others without the disorder (control group).
  • The PPID horses were then treated for 12 weeks either with pergolide or a placebo. The pergolide dose was adjusted based on monthly adenocorticotropin measurements. The same markers mentioned above were compared again after the 12 weeks of treatment.

Findings and Conclusion

  • The results showed a higher transcript abundance of muscle RING finger 1 (MuRF1) in PPID horses compared to the control group. This suggests an increase in proteolysis in these horses.
  • However, the pergolide treatment did not show any observable difference in transcript abundance of proteolysis markers, contradicting the original hypothesis.
  • Interestingly, the pergolide treated horses exhibited weight loss and improved fasting insulin regulation, while those given the placebo gained weight and rump fat thickness.
  • The major takeaway from this study is that despite the assumed impacts, pergolide treatment does not seem to affect muscle mass or markers of muscle proteolysis in horses with PPID. Instead, it may promote weight loss and improve insulin regulation.

Cite This Article

APA
Banse HE, Whitehead AE, McFarlane D, Chelikani PK. (2021). Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy. Domest Anim Endocrinol, 76, 106620. https://doi.org/10.1016/j.domaniend.2021.106620

Publication

ISSN: 1879-0054
NlmUniqueID: 8505191
Country: United States
Language: English
Volume: 76
Pages: 106620
PII: S0739-7240(21)00017-5

Researcher Affiliations

Banse, H E
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: hbanse1@lsu.edu.
Whitehead, A E
  • Department of Veterinary and Clinical Diagnostic Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada.
McFarlane, D
  • Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
Chelikani, P K
  • School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA.

MeSH Terms

  • Animals
  • Horse Diseases / metabolism
  • Horses
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / pathology
  • Muscular Atrophy / veterinary
  • Pergolide / therapeutic use
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate / metabolism

Citations

This article has been cited 2 times.
  1. Kirkwood NC, Hughes KJ, Stewart AJ. Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID).. Vet Sci 2022 Oct 17;9(10).
    doi: 10.3390/vetsci9100572pubmed: 36288186google scholar: lookup
  2. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup