Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.
Authors: Carmalt James L, Mortazavi Sima, McOnie Rebecca C, Allen Andrew L, Unniappan Suraj
Journal: PloS one
Summary
# Editorial Summary: POMC Processing and PPID Pathophysiology Equine pituitary pars intermedia dysfunction involves hyperplasia of melanotroph cells and excessive ACTH production, but the underlying biochemical mechanisms remain incompletely understood. Carmalt and colleagues investigated whether abnormal processing of pro-opiomelanocortin (POMC) contributes to PPID by examining mRNA expression of POMC and its processing enzymes (PC1 and PC2) in pituitaries from affected and control horses, alongside plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) concentrations. All three gene products—POMC, PC1, and PC2—were upregulated in PPID pituitaries, and whilst both ACTH and α-MSH were elevated in affected horses, the pattern suggested impaired conversion of ACTH to its further metabolite. These findings suggest that PPID involves not simply excessive POMC synthesis but also dysregulation of the enzymatic cascade that normally processes POMC into its active peptides, potentially explaining why some PPID horses present with disproportionately high ACTH despite elevated α-MSH. For practitioners, this work reinforces that PPID is a complex endocrine disorder affecting multiple steps in hormone metabolism rather than a single overproduction defect, which may inform future therapeutic strategies targeting prohormone processing pathways alongside dopamine agonism.
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Practical Takeaways
- •PPID involves dysregulation of hormone processing at the molecular level, not just simple hormone overproduction, which may inform future targeted therapeutic approaches
- •Elevated ACTH without proportional α-MSH elevation in PPID cases reflects impaired enzyme processing rather than simple pituitary failure
- •Understanding the specific molecular defects in PPID processing enzymes may help explain why some horses respond better to certain treatments than others
Key Findings
- •POMC, PC1, and PC2 mRNA expression are upregulated in pituitary tissue of horses with PPID compared to controls
- •Plasma ACTH and α-MSH concentrations are elevated in PPID horses despite upregulation of processing enzymes
- •Altered prohormone processing enzyme expression suggests local pituitary-specific dysfunction contributes to PPID pathogenesis
- •Inadequate conversion of ACTH to α-MSH by prohormone convertases may explain elevated circulating ACTH in PPID