In the lamprey, which is a member of the oldest extant class of vertebrates, the agnathans, melanotropins (MSH) and corticotropin (ACTH) were found to be encoded on two distinct genes. In all other vertebrates, a single precursor gene, proopiomelanocortin (POMC), encodes MSH and ACTH, as well as beta-endorphin (END). Two different cDNAs were cloned from a lamprey pituitary lambda gt11 cDNA library using antisera against lamprey MSH-B and ACTH(1-16). One cDNA encoded MSH-B, MSH-A and beta-END, while the other cDNA encoded nasohypophysial factor (NHF), ACTH and a different beta-END, but not MSH-A and MSH-B. Northern blot analysis demonstrated that in the adult lamprey pituitary, genes for MSH and ACTH are expressed in the pars intermedia (PI) and pars distalis (PD), respectively. (C) 1995 Academic Press, Inc.