Correlation of pituitary histomorphometry with dopamine and dopamine D2 receptor expression in horses with pituitary pars intermedia dysfunction.
Abstract: Pituitary pars intermedia dysfunction (PPID) is an endocrinopathy commonly affecting old horses. It is a spontaneously occurring, progressive disease that is still poorly understood. Previous studies have observed neurodegeneration of the dopaminergic inhibition of melanotrophs, which leads to decreased dopamine (DA) in the pars intermedia (PI) and increased pro-opiomelanocortin-derived peptides circulating in plasma. However, rats knockout for the dopamine D2 receptor (D2r) similarly develop PI hypertrophy and hyperplasia. Thus, based on the current pathophysiological theory of PPID, whether the decreased DA or the D2r dysfunction leads to PPID is still unclear. To test this, a total of 28 retrospective cases of horses with PPID were collected, graded and the expression of tyrosine hydroxylase (TH) and D2r in the PI were determined. The histological and immunohistochemical results demonstrated that horses with higher tumor histological grades had reduced TH expression with increased D2r immunoreactivity colocalized in the PI (p < 0.001, p < 0.05 respectively). This correlation supports the role of DA in the pathogenesis of continuous unregulated proliferation of neoplastic cells in PI and indicates the efficiency of D2r agonists as a treatment for PPID.
Copyright © 2022. Published by Elsevier Ltd.
Publication Date: 2022-08-24 PubMed ID: 36126509DOI: 10.1016/j.rvsc.2022.08.018Google Scholar: Lookup
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- Journal Article
- Aging
- Cell Proliferation
- Correlation Analysis
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Dopamine
- Endocrine System
- Equine Health
- Histology
- Horses
- Immunohistochemistry
- Neurodegenerative Disorders
- Pathophysiology
- Peptides
- Pituitary Pars Intermedia Dysfunction
- Plasma
- Retrospective Study
- Tumor
- Veterinary Medicine
- Veterinary Research
Summary
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This study investigates the correlation between pituitary gland abnormalities, and the expression of dopamine and dopamine D2 receptors in horses suffering from pituitary pars intermedia dysfunction (PPID). The findings suggest that decreased dopamine in these horses contributes to cell overgrowth in a region of the pituitary gland, and that doping D2 receptors could be an effective treatment.
Background and Objective
- This research aims to clarify whether decreased dopamine (a type of neurotransmitter) or dysfunction of dopamine D2 receptors (D2r) causes PPID, a common disorder in aging horses characterized by endocrine system malfunction.
- The scholars note that while previous studies have highlighted neurodegeneration leading to decreased dopamine in the PI and increased pro-opiomelanocortin-derived peptides in the bloodstream, it’s unclear whether this decrease in dopamine or D2r dysfunction is the primary contributor to PPID.
Methodology
- To examine this further, the researchers collected and examined 28 retrospective cases of horses with PPID.
- They graded these cases and determined the expression of tyrosine hydroxylase (TH, an enzyme that plays a critical role in dopamine production), and D2r in the PI.
Findings
- The histological and immunohistochemical analysis revealed that horses with higher tumor histological grades (indicating more severe disease) had reduced TH expression along with increased D2r immunoreactivity in the PI.
- The correlation between these findings supports the theory that Dopamine plays a significant role in controlling the proliferation of neoplastic (abnormal) cells in the PI.
- The increased Dopamine D2 receptor expression possibly suggests a compensatory response to decreased dopamine levels.
Conclusions
- Based on the correlated decrease of dopamine production and the increase of D2r in the pituitary gland, the researchers conclude that decreased dopamine could be a driving factor in the development of PPID.
- This indicates that D2r agonists (compounds that activate D2r) may be an effective treatment for PPID, offering potential new avenues for managing the condition in horses.
Cite This Article
APA
Huang L, Palmieri C, Bertin FR.
(2022).
Correlation of pituitary histomorphometry with dopamine and dopamine D2 receptor expression in horses with pituitary pars intermedia dysfunction.
Res Vet Sci, 152, 427-433.
https://doi.org/10.1016/j.rvsc.2022.08.018 Publication
Researcher Affiliations
- School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. Electronic address: luoyi.huang@uqconnet.edu.au.
- School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. Electronic address: c.palmieri@uq.edu.au.
- School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. Electronic address: f.bertin@uq.edu.au.
MeSH Terms
- Horses
- Animals
- Rats
- Dopamine / metabolism
- Retrospective Studies
- Horse Diseases / pathology
- Pituitary Diseases / genetics
- Pituitary Diseases / veterinary
- Pituitary Diseases / metabolism
- Receptors, Dopamine D2 / genetics
- Receptors, Dopamine D2 / metabolism
- Pituitary Gland, Intermediate / metabolism
- Pituitary Gland, Intermediate / pathology
- Rodent Diseases
Conflict of Interest Statement
Declaration of Competing Interest No conflicts of interest occurred to carry out this experiment.
Citations
This article has been cited 2 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).
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