Purification and biological characterisation of melanotrophins and corticotrophins

The remarkable conservation of the primary structures and anatomical location of dogfish a-melanocyte-stimulating hormone (MSH), corticotrophin-like intermediate lobe peptide (CLIP) and adrenocorticotrophic hormone (ACTH) compared with mammals reinforced the tissue-specific processing hypothesis of ACTH peptides in the pituitary gland. The cloning of dogfish pro-opiomelanocortin (POMC) led to the identification of delta-MSH and simultaneously revealed the high conservation of the gamma-MSH sequence during evolution. These studies have also shown that beta-MSH is much less conserved during evolution and in some species is not even processed from beta-LPH. Human pro-gamma-MSH potentiates the corticosteroidogenic activity of ACTH and peptides generated from its N-terminal, in particular big-gamma-MSH, appear to have adrenal mitogenic activity. Human big-gamma-MSH (from the zona intermedia) may also cause the adrenache. The review finishes with a cautionary note with regard to the misdiagnosis of the ectopic ACTH syndrome in which partial processing of ACTH can result in large concentrations of alpha-MSH and CLIP, which can interfere in the performance of two-site immunoassays, and the problem of the correct disulphide bridge arrangement in synthetic N-POMC peptides is also discussed.