title: Antigonadal effects of two novel melatonin analogues in adult Djungarian hamsters.
abstract: This study examined the effects of two novel melatonin analogues in adult Djungarian hamsters housed under long photoperiod (LD 16:8). Daily injection (10 micrograms, s.c.) of either melatonin, 5-methoxy N-butanoyltryptamine (bMT), or 5-methyl N-butanoyltryptamine (5-MebT) 3 hr before lights off for 8 weeks led to a significant decrease in paired testis weight compared to vehicle-injected controls. The reduction in testis weight was of similar magnitude with melatonin and bMT, but 5-MebT was not as effective. The affinity of the analogues was determined in competition experiments using chicken brain membranes and 2-[125I]iodomelatonin (2-[125I]aMT). Replacing the N-acetyl side-chain of melatonin with an N-butanoyl group increased affinity for the chicken brain 2-[125I]aMT binding site, but exchanging the 5-methoxy group of melatonin for a 5-methyl group reduced affinity. These studies show that these analogues not only inhibit 2-[125I]aMT binding in vitro but also mimic melatonin's antigonadal activity in vivo.
authors.affiliation: Biomedical Sciences Division, King's College London, Kensington, UK.
authors.forename: N W
authors.initials: NW
authors.lastname: Chong
authors.forename: D
authors.initials: D
authors.lastname: Sugden
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D006224:Cricetinae; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D017111:Phodopus; D017440:Photoperiod; D013737:Testis / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D014363:Tryptamines; C085309:N-butanoyl-5-methoxytryptamine; C085308:N-butanoyl-5-methyltryptamine; C044556:2-iodomelatonin; D008550:Melatonin