The coelacanth fish, genus Latimeria, flourished during the Devonian Period and is considered among the closest living relatives of tetrapods. It may therefore provide important information on the evolution of fishes into tetrapods. However, little is known about the components of the endocrine system in this fish. Here we describe the structural characterization of pituitary hormones derived from proopiomelanocortin (POMC) in Latimeria chalumnae. We identified alpha-melanocyte-stimulating hormone (MSH), N-Des-acetyl-alpha-MSH, beta-MSH, N-terminal peptide containing gamma-MSH, corticotropin-like intermediate lobe peptide (CLIP), and N-acetyl-beta-endorpin (END) in an extract from the rostral pars distalis of the pituitary by reversed-phase high-performance liquid chromatography, amino acid sequence analysis, and mass spectrometry. The occurrence of three different MSHs and one beta-END indicates that the structural organization of coelacanth POMC is the same as that of lungfish, tetrapods, and primitive ray-finned fish. The coelacanth alpha-MSH is identical to its mammalian counterpart. The coelacanth beta-MSH shows the highest sequence identity with the amphibian counterpart, and gamma-MSH and CLIP show the highest sequence identity with their amphibian and bird counterparts, whereas coelacanth beta-END is most similar to the sturgeon peptide. The coexistence of tetrapod-type and fish-type characteristics in the putative coelacanth POMC molecule reflects the phylogenetic position of this fish. When each hormonal segment was compared between coelacanth, lungfish, and tetrapod, MSH and CLIP of coelacanth were closer to their tetrapod counterparts than those of lungfish, whereas beta-MSH and P-END of coelacanth are less closely related to their tetrapod counterparts than those of lungfish. gamma-MSH and CLIP may have evolved at a different rate from beta-MSH and beta-END in both the coelacanth and lungfish. (C) 2003 Elsevier Science (USA). All rights reserved.