Melanin concentrating hormone (MCH): Structure-function aspects of its melanocyte stimulating hormone-like (MSH-like) activity

• Published in: Peptides (New York, N.Y. : 1980) Vol. 10; no. 4; pp. 773 - 778
• Main Authors: Matsunaga, Terry O, Hruby, Victor J, Lebl, Michal, Castrucci, Ana Maria De Lauro, Hadley, Mac E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1989
• Subjects: Amino Acid Sequence; Animals; Cell Aggregation - drug effects; Fishes; Hypothalamic Hormones; In Vitro Techniques; Lizards; Melanin concentrating hormone (MCH); Melanins - analysis; Melanins - chemical synthesis; Melanins - pharmacology; Melanocyte stimulating hormone-like activity; Melanocyte-Stimulating Hormones - chemical synthesis; Melanocyte-Stimulating Hormones - pharmacology; Melanocytes - drug effects; Molecular Sequence Data; Peptide Fragments - analysis; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Pituitary Hormones - chemical synthesis; Pituitary Hormones - pharmacology; Rana pipiens; Skin - drug effects; Skin Pigmentation - drug effects; Stereoisomerism; Structure-Activity Relationship; Structure-function aspects; Melanocyte stimulating hormone-like activity; Melanin concentrating hormone (MCH); Structure-function aspects
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/0196-9781(89)90112-5

Melanin concentrating hormone (MCH) is a heptadecapeptide, Asp-Thr-Met-Arg- Cys-Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys -Trp-Glu-Val, synthesized in the brain and secreted from the pars nervosa of teleost fish. This hormone stimulates melanosome (melanin granule) aggregation within integumental melanocytes of fishes but, in contrast, stimulates melansome dispersion within tetrapod (frog and lizard) melanocytes. We determined the message sequence of the primary structure of MCH which is responsible for its MSH-like component of activity. Removal of the N-terminal amino acid results in an almost total loss of MSH-like activity. The C-terminal amino acid is also essential for full MSH-like activity since the analogue, MCH(1–16), is about 100 times less active than MCH. Therefore, the entire heptadecapeptide sequence of MCH appears to contribute to the MSH-like activity of MCH. Ring-contracted analogues (e.g., [Ala 5,Cys 10]MCH) of MCH are almost devoid of any melanosome aggregating (MCH-like) activity but generally possess considerable or as great an MSH-like activity as MCH. Racemization of MCH by heat-alkali treatment drastically reduces the MCH-like activity of MCH, but does not enhance the MSH-like activity of the hormone.