Numerous papers published between 1930 and 1960 reported that extracts of teleost pituitary glands would induce pallor when injected into teleost recipients. It was, therefore, assumed that these pituitaries contained a paling hormone, variously called the melanophorecontracting or melanophore-aggregating hormone or MCH. Since melanin-dispersing bioactivity was also recognized in the teleost pituitary, the possibility of a bihumoral control of color change in some fishes was generally envisaged by 1957 when Pickford and Atz 1

published their excellent and comprehensive review of the literature. Nevertheless, MCH presented some puzzling features. In contrast to the widespread occurrence of MSH throughout the vertebrates, MCH seemed to occur in the pituitary gland only of teleost fish, and little, if any, comparable bioactivity was apparent in the pituitary gland of other vertebrates. Moreover, the melanin-concentrating response to fish pituitary extracts was not exhibited by all teleosts; some species responded by melanin dispersion, as did the melanophores from other groups of lower vertebrates. 1 The claim by one worker2 that a melanin-concentrating agent was present in the hypothalamus as well as in the pituitary gland of the catfish, Parasilurus was not immediately confirmed for other fish, 3 and attracted no further attention. Furthermore, separation of MCH and melanin-stimulating hormone (MSH) bioactivities proved capricious, I.4 and when the evidence for a bihumoral control of melanophores in amphibians could be reinterpreted in terms of a single melanotropin, 5 interest and credence in an MCH in fishes rapidly waned. It was two decades after Pickford's and Atz's book' that reinvestigation of the hormonal control of color change in fishes provided physiological evidence for the secretion of an MCH by the pituitary gland,6 and subsequent studies then led to the proposal, in support of Enami's earlier suggestion, that the hormone was a neurohypophysial peptide, synthesized by neurones in the hypothalamus and stored in the neural lobe of the pituitary. 7 ·8 The molecule from the salmonid pituitary gland has now been characterized and shown to be a cyclic heptadecapeptide, 9 while immunocytochemical studies have confirmed its synthesis by neurones in the nucleus lateralis tuberis (NL T) of the ventral hypothalamus. 10 Bioassays, and more recent immunocytochemical studies, have shown that the molecule is present in the brain, but not always the pituitary, of many classes of vertebrate from lampreys to mammals (Section III). In teleosts, amphibians, and mammals, fibers from the immunoreactive cell bodies extend into extrahypothalamic regions of the brain, presumably exerting a neuromodulatory function. Even in teleosts, the biological effects of MCH are not restricted to pigmentary control at the level of the melanophores but include also the inhibition of MSH and adrenocorticotropin (ACTH) release from the pituitary gland (Section VII). Thus, although the molecule is termed MCH because of its role in teleost fish in which it was first discovered, it seems likely that this function is an evolutionary specialization confined to teleosts, and that its role as a neuromodulator and as an hypophysial regulatory hormone may be of more widespread importance.