Natural occurrence but lack of melanotrophic activity of γ-MSH in fish

Abstract

When adrenocorticotropin (ACTH) and β-lipotropin (LPH) are enzymatically cleaved in the pituitary from their common precursor molecule, a glycopeptide with an apparent molecular weight of 16,000 remains (reviewed in ref. 1). Sequencing of a cDNA copy of the bovine pituitary mRNA for the precursor molecule demonstrated that, within the region encoding the 16,000-moIecular weight (MW) glycopeptide, there was a short sequence homologous with the α-melanocyte-stimulating hormone (α-MSH) contained in ACTH and the β-MSH within β-LPH². It was therefore proposed that the region of homology coded for a γ-MSH which might have biological activity, although synthetic peptides containing this sequence were shown to have poor melanotrophic activity³. In the pars intermedia further rapid enzyme modification converts ACTH to α-MSH and corticotropin-like intermediate lobe peptide (CLIP), and β-LPH to β-MSH and β-endorphin. Although smaller peptides containing the γ-MSH structure have been detected in extracts of the bovine pars intermedia^4,5, the major post-translational products of the 16,000-MW fragment are present mainly as large glycosylated peptides^1,4. We report here that a major peptide product of the neurointermediate lobe of the dogfish pituitary which we had previously shown to lack melanotrophic activity has a γ-MSH-like structure. Therefore if γ-MSH is a peptide with a function it is not one shared with the melanotrophic hormones.