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Equine Cushing’s disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary.
Abstract: Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels of circulating glucocorticoids inhibit POMC biosynthesis in corticotrophs. Although the i beta-endorphin concentration of the tumors was not different from that in normal tissue, the posttranslational processing of beta-endorphin in the two tissues differed significantly. In controls, beta-endorphin-(1-31) was extensively processed to N-acetyl-beta-endorphin-(1-31), -(1-27), and -(1-26) and des-acetyl beta-endorphin-(1-27). N-Acetyl-beta-endorphin-(1-27) was the predominant form, constituting 57% of the total i beta-endorphin, whereas beta-endorphin-(1-31) was quantitatively minor (less than 7% of the total immunoreactivity. In adenomatous pituitaries, the processing of beta-endorphin was restricted, significantly increasing the proportions of beta-endorphin-(1-31) and N-acetyl-beta-endorphin-(1-31) and lowering the amounts of N-acetyl-beta-endorphin-(1-27) and -(1-26). These changes in peptide processing were associated with markedly reduced levels of dopamine, suggesting that the dopaminergic neurons that normally control intermediate lobe secretion no longer innervate the hyperplastic tissue. These findings are consistent with evidence that the dopaminergic innervation of the intermediate pituitary regulates the posttranslational processing and release of beta-endorphin.
Publication Date: 1988-09-01 PubMed ID: 2456916DOI: 10.1210/endo-123-3-1598Google 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
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study investigates the altered processing of the hormone beta-endorphin in the pituitary gland of horses with Cushing’s disease, a condition characterized by an overactive pituitary gland secreting high levels of hormones. It is observed that while the concentration of beta-endorphin remained constant, its post-production processing was significantly different, correlating with significantly reduced levels of dopamine.
Research Background
- Cushing’s disease in horses results from an abnormal enlargement (hyperplasia) of the intermediate pituitary – a part of the brain that secretes hormones.
- This condition is associated with high secretion levels of hormone beta-endorphin, ACTH, and other hormones derived from POMC.
Research Findings
- Testing revealed highly elevated levels of plasma and cerebrospinal fluid beta-endorphin (i beta-endorphin) in horses affected with Cushing’s disease compared to control subjects.
- While the levels of i beta-endorphin in the intermediate and anterior lobe of pituitary gland showed no significant differences, it was found that the concentration of beta-endorphin in the anterior lobe was significantly lower in Cushing’s disease affected horses.
- This decrease is postulated to be due to high levels of circulating glucocorticoids, which hinder POMC biosynthesis in corticotrophs (cells responsible for ACTH production).
- Although the concentration of i beta-endorphin in the pituitary tumors was consistent with the normal tissue, the post-production modification (posttranslational processing) of beta-endorphin significantly varied in the two tissues.
- In the afflicted horses, there was limited processing of beta-endorphin. This led to an increased proportion of certain forms of beta-endorphin and reduced amounts of others.
- These changes in the processing of this hormone were associated with significantly reduced levels of dopamine, indicating a probable loss in the function of dopaminergic neurons that typically regulate hormone secretion in the intermediate pituitary lobe.
Implications of Findings
- The altered hormone processing indicates a role of dopaminergic neurons in controlling the posttranslational processing and release of beta-endorphin.
- These findings further our understanding of the biochemical changes in equine Cushing’s disease and can assist in developing new therapeutic approaches or early diagnosis methods for this condition.
Cite This Article
APA
Millington WR, Dybdal NO, Dawson R, Manzini C, Mueller GP.
(1988).
Equine Cushing’s disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary.
Endocrinology, 123(3), 1598-1604.
https://doi.org/10.1210/endo-123-3-1598 Publication
Researcher Affiliations
- Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
MeSH Terms
- 3,4-Dihydroxyphenylacetic Acid / metabolism
- Animals
- Cushing Syndrome / etiology
- Cushing Syndrome / metabolism
- Cushing Syndrome / veterinary
- Dopamine / metabolism
- Female
- Horse Diseases / metabolism
- Horses
- Hydroxyindoleacetic Acid / metabolism
- Male
- Orchiectomy
- Pituitary Gland / metabolism
- Pituitary Neoplasms / metabolism
- Pituitary Neoplasms / veterinary
- Protein Processing, Post-Translational
- Reference Values
- Serotonin / metabolism
- beta-Endorphin / blood
- beta-Endorphin / cerebrospinal fluid
- beta-Endorphin / genetics
Citations
This article has been cited 8 times.- Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
- Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott HC 2nd. Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy. Sci Rep 2021 Aug 6;11(1):16036.
- Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stöckle SD. Pituitary Pars Intermedia Dysfunction and Metabolic Syndrome in Donkeys. Animals (Basel) 2020 Dec 8;10(12).
- Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T. Metabolic changes induced by oral glucose tests in horses and their diagnostic use. J Vet Intern Med 2021 Jan;35(1):597-605.
- Fortin JS, Benskey MJ, Lookingland KJ, Patterson JS, Howey EB, Goudreau JL, Schott HC 2nd. Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction. BMC Vet Res 2020 Sep 25;16(1):356.
- Carmalt JL, Mortazavi S, McOnie RC, Allen AL, Unniappan S. Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction. PLoS One 2018;13(1):e0190796.
- Carmalt JL, Scansen BA. Development of two surgical approaches to the pituitary gland in the Horse. Vet Q 2018 Dec;38(1):21-27.
- Haritou SJ, Zylstra R, Ralli C, Turner S, Tortonese DJ. Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod. J Neuroendocrinol 2008 Aug;20(8):988-96.
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