43 Moreover, in sheep, melatonin Apoptosis Compound Library implants in the mediobasal hypothalamus block the effects of SP on LH but not on prolactin, while implants close to the PT inhibit prolactin secretion.44 Interestingly, melatonin binding sites have been detected in the DMH in the Syrian hamster, although with a very

low density, and their density depends on the photoperiod (Pévet P et al, unpublished data). The hypothesis of a parallel and concomitant action of melatonin on different structures to transduce the photoperiodic message is attractive. The photoperiod is known, through changes in duration of melatonin secretion, to control not only the reproductive annual cycle, but also a large number of other Inhibitors,research,lifescience,medical seasonal functions (eg, body weight, hibernation, daily torpor, fur color changes, and migration). Furthermore, not all seasonal functions are Inhibitors,research,lifescience,medical expressed in every species and different control mechanisms may be involved. For example, SP induces an activation of the sexual axis in sheep, but inhibition

in Syrian and Siberian hamsters; and hibernation in the Syrian hamster is directly dependent on photoperiod, while in the Ruropean hamster it is dependent on a “circannual clock” entrained by photoperiod. It thus seems likely that melatonin acts at different structures according to the species and the Inhibitors,research,lifescience,medical function. This concept would account for the large interspecies differences observed in mammals in the distribution of structures containing melatonin receptors. Interestingly, and in support of this concept, a pharmacological dissociation of photopcriodic-controlled Inhibitors,research,lifescience,medical seasonal functions has been reported. S 22153, a melatonin antagonist of MT1 and MT2 melatonin receptor subtypes, caused a decrease in the duration of hibernation in Syrian hamsters under SP and low temperature, but Inhibitors,research,lifescience,medical did not affect SP-induced gonadal atrophy.45 Melatonin and circadian function In most nonmammalian vertebrates, the rhythmic synthesis and secretion of melatonin is the direct output of circadian clock, and the rhythmic changes in the concentration of circulating

melatonin are fundamental to circadian rhythmicity.46 In mammals, despite the presence Thiamine-diphosphate kinase of melatonin receptors in the SCN of most species indicating hormonal feedback on the clock, the consensus has been that melatonin has only a limited role in circadian organization. This view has arisen, in part, since pinealectomy has little effect on circadian organization.47 Melatonin rhythm, however, is only one of the outputs of the clock and it is probable that, for the organization of circadian activities, a number of different output signals from the clock are involved in the distribution of circadian information to target tissues.48,49 This does not preclude an important role for melatonin in circadian organization.