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Proopiomelanocortin-derived peptides

X Bertagna1

  • 1Clinique des Maladies Endocriniennes, Hôpital Cochin, Paris, France.

Endocrinology and Metabolism Clinics of North America
|September 1, 1994
PubMed
Summary

Pro-opiomelanocortin (POMC) is a precursor protein that yields various peptides, including ACTH. Differential processing by prohormone convertases (PC1 and PC2) in pituitary cells generates distinct peptide profiles, impacting their measurement in blood.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Background:

  • Pro-opiomelanocortin (POMC) is a precursor polypeptide processed into various biologically active peptides, including adrenocorticotropic hormone (ACTH).
  • The cloning of POMC mRNA established molecular links between ACTH, beta-lipotropin (beta-LPH), gamma-lipotropin (gamma-LPH), and beta-endorphin.
  • Previously unidentified POMC-derived peptides, such as the N-terminal fragment and joining peptide (JP), have also been characterized.

Purpose of the Study:

  • To elucidate the molecular basis of POMC processing and the resulting peptide products.
  • To understand the differential roles of prohormone convertases (PC1 and PC2) in POMC cleavage within different pituitary cell types.
  • To explore the physiological significance and measurement of POMC peptides in human circulation.

Main Methods:

  • Characterization of POMC mRNA and its derived peptides through cDNA cloning.
  • Investigation of prohormone convertase specificities (PC1 and PC2) in POMC proteolysis.
  • Development of radioimmunoassay (RIA) and immunoradiometric assay (IRMA) for POMC peptide detection in blood.

Main Results:

  • POMC processing yields distinct peptide profiles in the anterior pituitary (corticotrophs) versus the intermediate pituitary (melanotrophs) due to differential PC1 and PC2 expression.
  • While ACTH is the primary identified functional peptide, other POMC-derived peptides are released equimolarly into circulation.
  • Disruptions in POMC processing, observed in conditions like renal failure or tumors, can alter peptide correlations and lead to the secretion of intact POMC or abnormal fragments.

Conclusions:

  • The processing of POMC is a complex, cell-specific event regulated by prohormone convertases, generating a family of peptides with varying physiological roles.
  • Measurement of POMC peptides, particularly LPH, serves as a reliable indicator of corticotroph function, although pathological conditions can disrupt this correlation.
  • Advanced assays like IRMA enable the direct detection of unprocessed POMC, offering new diagnostic possibilities for disorders of POMC metabolism.

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