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Endocrinology1982; 110(3); 941-954; doi: 10.1210/endo-110-3-941

Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing’s horses.

Abstract: Using RIAs for six regions within proopiolipomelanocortin (proOLMC), gel filtration, and electrophoresis, we studied pituitary peptides in a normal horse and one with Cushing's disease caused by a pars intermedia adenoma. Almost all immunoreactive (IR) ACTH (78%) was 4,500 mol wt (4.5K) ACTH in normal pars distalis, but it was almost 100% corticotropin-like intermediate lobe peptide (CLIP) in normal pars intermedia. alpha MSH and beta MSH were found mainly in pars intermedia: equal concentrations of the beta MSH precursors, beta-lipotropin (beta LPH) and gamma LPH, were found in pars distalis. Most IR-beta-endorphin (IR-beta END) was found as beta END in pars intermedia, but roughly equal concentrations of beta END and its precursor, beta LPH, were found in pars distalis. A 33K molecule containing IR-ACTH, IR-gamma 3MSH, and IR-beta END, presumed to be proOLMC, and a variety of 15-27K presumed biosynthetic intermediates were found in both normal pars distalis and pars intermedia. The pars intermedia adenoma causing Cushing's syndrome contained high IR-peptide concentrations. Several differences in precursors were noted, including the presence of three larger presumed precursors (38.5K, 47K, and 63K) that had both ACTH and beta END immunoreactivities and both deletions and additions of 15-27K intermediates. The Cushing's horse's plasma peptides reflected tumor concentrations; 4.5K ACTH was modestly elevated, but the concentrations of CLIP, alpha MSH, beta MSH, gamma LPH, and beta END were dramatically increased. About 20% of plasma IR-ACTH and 5% of IR-beta MSH and IR-beta END were found as high molecular weight forms. Normal processing of horse proOLMC appears to be similar to that in other species, but may be altered in pars intermedia tumors of horses with Cushing's disease, the plasma of which contains disproportionately increased concentrations of pars intermedia proOLMC peptides.
Publication Date: 1982-03-01 PubMed ID: 6276164DOI: 10.1210/endo-110-3-941Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The research article deals with understanding the distribution and concentration of peptides originating from the proopiolipomelanocortin (proOLMC) protein in normal horses and those suffering from Cushing’s disease, a condition caused by hormonal imbalance. Standardized biochemical techniques are used to identify and analyze these peptides in the pituitary gland (a gland responsible for producing key hormones) and blood plasma of both types of horses.

Techniques Employed

  • The researchers used radioimmunoassay (RIA) for six regions within proopiolipomelanocortin (proOLMC). This technique is used to measure the concentration of specific antigens by using their known antibodies.
  • Gel filtration – also known as size exclusion chromatography is used to separate biomolecules based on their size.
  • Electrophoresis is a laboratory technique used for separating biomolecules such as proteins and nucleic acids based on their size and electrical charge.

Findings in Normal Horse

  • In a normal horse, almost all of the immunoreactive ACTH (a hormone that regulates the stress response) was identified as 4500 molecular weight ACTH in the normal pars distalis section of the pituitary gland.
  • In the normal pars intermedia section of the pituitary gland, the ACTH was mostly corticotropin-like intermediate lobe peptide (CLIP).
  • Peptides alpha MSH and beta MSH were mainly found in pars intermedia with equal concentrations of beta-lipotropin (beta LPH) and gamma LPH (both precursors to MSH) in pars distalis.
  • The majority of IR-beta-endorphin (a pain-relieving hormone) was found as beta END in pars intermedia with equal amounts of beta END and its precursor, beta LPH, found in pars distalis.

Findings in Cushing’s Disease Affected Horse

  • The adenoma (a benign tumor) in the pars intermedia region that caused Cushing’s disease contained high concentrations of immunoreactive peptides.
  • Differences in precursors were observed, including the presence of larger precursors with both ACTH and beta END immunoreactivity; there were changes in the 15-27K intermediates too.
  • Plasma peptides in the diseased horse reflected tumor concentrations, with an increase in the concentration of several peptides including CLIP, alpha MSH, beta MSH, gamma LPH, and beta-END.

Inference

  • Proopiolipomelanocortin peptides processing in a healthy horse seemed similar to other species.
  • In horses with Cushing’s disease, the processing could be altered, resulting in increased concentrations of these peptides in their blood plasma.

Cite This Article

APA
Wilson MG, Nicholson WE, Holscher MA, Sherrell BJ, Mount CD, Orth DN. (1982). Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing’s horses. Endocrinology, 110(3), 941-954. https://doi.org/10.1210/endo-110-3-941

Publication

ISSN: 0013-7227
NlmUniqueID: 0375040
Country: United States
Language: English
Volume: 110
Issue: 3
Pages: 941-954

Researcher Affiliations

Wilson, M G
    Nicholson, W E
      Holscher, M A
        Sherrell, B J
          Mount, C D
            Orth, D N

              MeSH Terms

              • Adrenocorticotropic Hormone / analysis
              • Animal Diseases / metabolism
              • Animals
              • Cushing Syndrome / metabolism
              • Cushing Syndrome / veterinary
              • Horses
              • Melanocyte-Stimulating Hormones / analysis
              • Pituitary Gland / analysis
              • Pituitary Hormones, Anterior / analysis
              • Pituitary Hormones, Anterior / blood
              • Pituitary Neoplasms / analysis
              • Pro-Opiomelanocortin
              • Protein Precursors / analysis
              • Protein Precursors / blood
              • Reference Values

              Grant Funding

              • 5-R01-CA-11685 / NCI NIH HHS
              • 5-R25-CA-19429 / NCI NIH HHS

              Citations

              This article has been cited 8 times.
              1. 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).
                doi: 10.3390/vetsci9100572pubmed: 36288186google scholar: lookup
              2. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
                doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
              3. 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).
                doi: 10.3390/ani10122335pubmed: 33302557google scholar: lookup
              4. Banse HE, Schultz N, McCue M, Geor R, McFarlane D. Comparison of two methods for measurement of equine adrenocorticotropin. J Vet Diagn Invest 2018 Mar;30(2):233-237.
                doi: 10.1177/1040638717752216pubmed: 29284383google scholar: lookup
              5. Oka Y, Orth DN. Human plasma epidermal growth factor/beta-urogastrone is associated with blood platelets. J Clin Invest 1983 Jul;72(1):249-59.
                doi: 10.1172/jci110964pubmed: 6603475google scholar: lookup
              6. Orth DN, Jackson RV, DeCherney GS, DeBold CR, Alexander AN, Island DP, Rivier J, Rivier C, Spiess J, Vale W. Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. J Clin Invest 1983 Mar;71(3):587-95.
                doi: 10.1172/jci110804pubmed: 6298280google scholar: lookup
              7. Menzies-Gow NJ. Equine Pituitary Pars Intermedia Dysfunction. Vet Sci 2025 Aug 20;12(8).
                doi: 10.3390/vetsci12080780pubmed: 40872730google scholar: lookup
              8. Zaidi M, Yuen T, Kim SM. Pituitary crosstalk with bone, adipose tissue and brain. Nat Rev Endocrinol 2023 Dec;19(12):708-721.
                doi: 10.1038/s41574-023-00894-5pubmed: 37715028google scholar: lookup