Melanin concentrating hormone (MCH): structure-function aspects of its melanocyte stimulating hormone-like (MSH-like) activity.
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 melanosome 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., [Ala5, Cys10]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.
Matsunaga
T O
TO
Department of Chemistry, University of Arizona, Tucson 85721.
Hruby
V J
VJ
Lebl
M
M
Castrucci
A M
AM
Hadley
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D005399:Fishes; D007028:Hypothalamic Hormones; D066298:In Vitro Techniques; D008116:Lizards; D008543:Melanins / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D009074:Melanocyte-Stimulating Hormones / Q000138:chemical synthesis / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology; D010907:Pituitary Hormones / Q000138:chemical synthesis / Q000494:pharmacology*; D011894:Rana pipiens; D012867:Skin / Q000187:drug effects*; D012880:Skin Pigmentation / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007028:Hypothalamic Hormones; D008543:Melanins; D010446:Peptide Fragments; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D009074:Melanocyte-Stimulating Hormones