Structural and functional diversity of proopiomelanocortin in fish with special reference to barfin flounder

Proopiomelanocortin (POMC) is a precursor of adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone (MSH), and endorphin (END). We have characterized POMC systems in barfin flounder. The results revealed unique aspects of POMC systems. Notable features in terms of pituitary functions are the occurrence of three functional POMC genes, the mutation of an essential sequence in the beta-END in one of the genes, occurrence of alpha-MSH in addition to ACTH in the pars distalis of the pituitary, and expression of the three genes in a single cell. While MSHs stimulate pigment dispersion, expression of the POMC gene and plasma levels of MSH do not always respond to background color changes between black and white. The functions of MSHs in skin pigmentation are very unique, because acetylation at the N-terminal of alpha-MSH inhibits its pigment dispersing activity. This is in contrast to results from other teleosts and amphibians, in which acetylation increases the activity. In the skin, the POMC gene is expressed in the non-chromatophoric dermal cells, indicating that MSH produced in the skin de novo has a paracrine function. The detection of MSH peptides in skin extracts seems to show that the control of skin pigmentation by MSHs is twofold-endocrine control by the pituitary, and paracrine control by the skin itself. Thus, fish provide an interesting model to help understand the structural and functional diversity of POMC systems. In this review, we provide an overview of our recent studies on the characterization of molecules and biological significance of POMC systems in barfin flounder.