CLONING AND CHARACTERIZATION OF A MAMMALIAN MELATONIN RECEPTOR THAT MEDIATES REPRODUCTIVE AND CIRCADIAN RESPONSES

The pineal hormone melatonin regulates seasonal reproductive function and modulates circadian rhythms in mammals. We now report the cloning and characterization of a high affinity receptor for melatonin from th e sheep and human. The receptor cDNAs encode proteins that are members of a newly discovered group within the G protein-coupled receptor fam ily. Expression of the sheep and human receptors in COS-7 cells result s in high affinity 2-[I-125]iodomelatonin binding and pharmacological characteristics similar to endogenous high affinity receptors. Functio nal studies of NIH 3T3 cells stably expressing the sheep receptor show that the mammalian melatonin receptor is coupled to inhibition of ade nylyl cyclase through a pertussis toxin-sensitive mechanism. In situ h ybridization studies of melatonin receptor mRNA in several mammals rev eal hybridization signals in the hypophyseal pars tuberalis and hypoth alamic suprachiasmatic nucleus. The cloned high affinity receptor like ly mediates the reproductive and circadian actions of melatonin in mam mals.