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Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.
Abstract: Equine pituitary pars intermedia dysfunction (PPID) is characterized by hyperplasia of the pars intermedia (PI) melanotrophs of the pituitary gland (PG), and increased production of proopiomelanocortin (POMC). POMC is cleaved by prohormone convertase 1 (PC1) to produce adrenocorticotropic hormone (ACTH), and further processing of ACTH by PC2 to produce alpha-melanocyte stimulating hormone (α-MSH) and corticotropin-like intermediate peptide (CLIP). High plasma ACTH concentrations in horses with PPID might be related to reduced conversion of ACTH to α-MSH by PCs. The hypothesis of this study was that PC1 and PC2 expression in the pituitary gland are altered in PPID, resulting in an abnormal relative abundance of POMC derived proteins. The objectives of this study were to identify the partial sequences of equine POMC, PC1, and PC2 mRNAs; and to determine whether the expression of POMC, PC1, and PC2 mRNAs in whole pituitary extracts, and POMC-protein in the cavernous sinus blood of horses are altered in PPID. We confirmed (RT-PCR and sequencing) that the partial sequences obtained match the corresponding regions of predicted equine POMC, PC1 and PC2 sequences. The expression (quantification by RT-qPCR) of POMC, PC1 and PC2 mRNAs were found upregulated in the pituitary of horses with PPID. Plasma (measured using RIA/ELISA) ACTH and α-MSH were elevated in PPID horses. These results indicate distinct differences in gene and protein expression of POMC and its intermediates, and processing enzymes in PPID. It provides evidence to support the notion that local, pituitary-specific inadequacies in prohormone processing likely contribute to equine PPID.
Publication Date: 2018-01-08 PubMed ID: 29309431PubMed Central: PMC5757946DOI: 10.1371/journal.pone.0190796Google 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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This study explores the changes in proopiomelanocortin (POMC) proteins and their related processing enzymes in horses with a pituitary gland disorder known as equine pituitary pars intermedia dysfunction (PPID). Remarkable differences are found in gene and protein expression levels of POMC and its components, suggesting that the malfunctioning of the pituitary gland is a significant contributor to the development of equine PPID.
Understanding Equine Pituitary Pars Intermedia Dysfunction (PPID)
- Equine PPID is a disorder that results in the abnormal growth of melanotroph cells in the pituitary gland, known as the pars intermedia (PI).
- Resultantly, the production of POMC by the pituitary gland is elevated. POMC is a prohormone that is typically processed into various other hormones.
The Role of Proopiomelanocortin (POMC) and Prohormone Convertases (PCs)
- POMC yields hormones such as adrenocorticotropic hormone (ACTH) when cleaved by prohormone convertase 1 (PC1).
- Further processing by PC2 generates alpha-melanocyte stimulating hormone (α-MSH) and corticotropin-like intermediate peptide (CLIP).
- Increased blood levels of ACTH in horses with PPID have been hypothesized to be due to a decrease in conversion from ACTH to α-MSH by PCs.
Objective and Results of the Study
- The scientists posited that changes in PC1 and PC2 expression in horses with PPID result in abnormal ratios of POMC-derived proteins due to altered hormone processing.
- For this purpose, the researchers identified partial sequences of POMC, PC1, and PC2 mRNAs and then examined whether their mRNA and protein expression levels in pituitary gland extracts and blood samples were changed in horses with PPID.
- The sequences obtained matched predicted equine versions of POMC, PC1, and PC2 sequences, substantiating the researchers’ hypothesis that the expression of these mRNAs were indeed upregulated in the pituitaries of PPID horses.
- Measurements of ACTH and α-MSH in the plasma further revealed increased levels of these hormones in PPID horses. This suggests that this disorder is characterized by distinct differences in the gene and protein expression of POMC and its components and the operation of processing enzymes.
Implications of the Study
- These results provide evidence supporting the belief that abnormalities in prohormone processing within the pituitary gland are likely contributors to equine PPID.
- This research could be instrumental in developing new treatments and prevention strategies for this disorder in horses.
Cite This Article
APA
Carmalt JL, Mortazavi S, McOnie RC, Allen AL, Unniappan S.
(2018).
Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.
PLoS One, 13(1), e0190796.
https://doi.org/10.1371/journal.pone.0190796 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
- Department of Veterinary Biomedical Sciences, Laboratory of Integrative Neuroendocrinology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
- Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
- Department of Veterinary Biomedical Sciences, Laboratory of Integrative Neuroendocrinology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
MeSH Terms
- Adrenocorticotropic Hormone / blood
- Amino Acid Sequence
- Animals
- Enzyme-Linked Immunosorbent Assay
- Horses
- Peptides / metabolism
- Pituitary Gland, Intermediate / enzymology
- Pituitary Gland, Intermediate / metabolism
- Pro-Opiomelanocortin / blood
- Pro-Opiomelanocortin / chemistry
- Pro-Opiomelanocortin / genetics
- Pro-Opiomelanocortin / metabolism
- Proprotein Convertase 1 / genetics
- Proprotein Convertase 1 / metabolism
- Proprotein Convertase 2 / genetics
- Proprotein Convertase 2 / metabolism
- RNA, Messenger / metabolism
- Sequence Homology, Amino Acid
- alpha-MSH / blood
Conflict of Interest Statement
Competing Interests: The authors have declared that no competing interests exist.
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Citations
This article has been cited 5 times.- 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).
- Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
- Hinrichsen SL, Yuen KY, Dryburgh EL, Bertin FR, Stewart AJ. Short-Term Effects of Temperature and Thyrotropin-Releasing Hormone Stimulation on Adrenocorticotropin Stability in Horses. Animals (Basel) 2022 Jan 28;12(3).
- Nitzsche AM, Fey K, Büttner K, Gröf M, Staszyk C. The Gingiva of Horses With Pituitary Pars Intermedia Dysfunction: A Macroscopic Anatomical Evaluation. Front Vet Sci 2021;8:786971.
- Hu K, Stewart AJ, Yuen KY, Hinrichsen S, Dryburgh EL, Bertin FR. The effect of freeze-thaw cycles on determination of immunoreactive plasma adrenocorticotrophic hormone concentrations in horses. J Vet Intern Med 2020 May;34(3):1350-1356.
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