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
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- Journal Article
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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.
References
This article includes 16 references
- McGowan TW, Pinchbeck GP, McGowan CM. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses.. Equine Vet J 2013 Jan;45(1):74-9.
- Millington WR, Dybdal NO, Dawson R Jr, Manzini C, Mueller GP. Equine Cushing's disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary.. Endocrinology 1988 Sep;123(3):1598-604.
- McFarlane D, Dybdal N, Donaldson MT, Miller L, Cribb AE. Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction.. J Neuroendocrinol 2005 Feb;17(2):73-80.
- Gehlert DR, Bishop JF, Schafer MP, Chronwall BM. Rat intermediate lobe in culture: dopaminergic regulation of POMC biosynthesis and cell proliferation.. Peptides 1988;9 Suppl 1:161-8.
- Engler D, Pham T, Liu JP, Fullerton MJ, Clarke IJ, Funder JW. Studies of the regulation of the hypothalamic-pituitary-adrenal axis in sheep with hypothalamic-pituitary disconnection. II. Evidence for in vivo ultradian hypersecretion of proopiomelanocortin peptides by the isolated anterior and intermediate pituitary.. Endocrinology 1990 Oct;127(4):1956-66.
- Saiardi A, Borrelli E. Absence of dopaminergic control on melanotrophs leads to Cushing's-like syndrome in mice.. Mol Endocrinol 1998 Aug;12(8):1133-9.
- Orth DN, Holscher MA, Wilson MG, Nicholson WE, Plue RE, Mount CD. Equine Cushing's disease: plasma immunoreactive proopiolipomelanocortin peptide and cortisol levels basally and in response to diagnostic tests.. Endocrinology 1982 Apr;110(4):1430-41.
- Irvine CH, Alexander SL. A novel technique for measuring hypothalamic and pituitary hormone secretion rates from collection of pituitary venous effluent in the normal horse.. J Endocrinol 1987 May;113(2):183-92.
- Klein C, Rutllant J, Troedsson MH. Expression stability of putative reference genes in equine endometrial, testicular, and conceptus tissues.. BMC Res Notes 2011 Apr 12;4:120.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
- Cordero M, Brorsen BW, McFarlane D. Circadian and circannual rhythms of cortisol, ACTH, and α-melanocyte-stimulating hormone in healthy horses.. Domest Anim Endocrinol 2012 Nov;43(4):317-24.
- Samuels ME, Gallo-Payet N, Pinard S, Hasselmann C, Magne F, Patry L, Chouinard L, Schwartzentruber J, René P, Sawyer N, Bouvier M, Djemli A, Delvin E, Huot C, Eugene D, Deal CL, Van Vliet G, Majewski J, Deladoëy J. Bioinactive ACTH causing glucocorticoid deficiency.. J Clin Endocrinol Metab 2013 Feb;98(2):736-42.
- Couëtil L, Paradis MR, Knoll J. Plasma adrenocorticotropin concentration in healthy horses and in horses with clinical signs of hyperadrenocorticism.. J Vet Intern Med 1996 Jan-Feb;10(1):1-6.
- Beech J, Boston RC, Lindborg S, Russell GE, McFarlane D, Lindborg S. Equine Cushing’s disease: plasma immunoreactive proopiolipomelanocortin peptide and cortisol levels basally and in response to diagnostic tests. J Am Vet Med Assoc 2013;27(1):73–80.
- Lee ZY, Zylstra R, Haritou SJ. The use of adrenocorticotrophic hormone as a potential biomarker of pituitary pars intermedia dysfunction in horses.. Vet J 2010 Jul;185(1):58-61.
- McFarlane D, Beech J, Cribb A. Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.. Domest Anim Endocrinol 2006 May;30(4):276-88.
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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