Dataset Information

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 (?-MSH) and corticotropin-like intermediate peptide (CLIP). High plasma ACTH concentrations in horses with PPID might be related to reduced conversion of ACTH to ?-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 ?-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.

SUBMITTER: Carmalt JL

PROVIDER: S-EPMC5757946 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.

Carmalt James L JL Mortazavi Sima S McOnie Rebecca C RC Allen Andrew L AL Unniappan Suraj S

PloS one 20180108 1

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 P ...[more]

PMID: 29309431

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Project description:Pituitary pars intermedia dysfunction (PPID) is the most prevalent endocrine disorder of older equids. To date, key research areas likely to have the greatest impact on equine health have not been identified. In human medicine, public and patient involvement is widely used to inform research agendas. This study aimed to engage with veterinary surgeons and horse owners to identify evidence gaps ('uncertainties') and prioritise these into a list of the 10 most important PPID research questions. The James Lind Alliance (JLA) Priority Setting Partnership (PSP) Framework was adapted. Questions about the diagnosis, treatment and prognosis of PPID were gathered via an online survey targeting veterinary surgeons and horse owners with experience of PPID. Thematic analysis was used to form a longlist of collated indicative research questions (CIRQs), defined by the JLA as true 'evidence uncertainties' when not answered by a published, clinically relevant, up-to-date systematic review. In an interim prioritisation survey, questions were ranked by weighted scores creating a shortlist of 25 that were taken forward to the PSP workshop, where participants reached a consensus on the top 10. Useable responses containing ≥1 question were received from 524 respondents (92.6% owners, n = 485; 7.4% veterinary surgeons, n = 39). After screening for relevance, 1,260 individual questions were included in thematic analysis, resulting in 47 CIRQs. Interim prioritisation votes for the CIRQs were received from 360 respondents. The top 10 questions prioritised at the PSP workshop focused on long-term prognosis, diagnostic accuracy, efficacy of pergolide treatment, alternative treatment/management strategies and potential treatment options for poor responders to pergolide. The quantity of questions generated indicates an extensive number of uncertainties regarding the diagnosis, treatment and prognosis of PPID. The top 10 research questions will help to inform key areas for evidence synthesis and knowledge translation, and to direct future research into areas most important to end users involved in caring for and treating animals with PPID.

Dataset Information

Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.

Publications

Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.

Similar Datasets

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