ABSTRACT
M elatonin is a hormone produced in the pineal gland o f vertebrates. W hile early medical textbooks often referred to the pineal gland as a vestigial organ in m am mals, the discovery o f melatonin by Aaron Lem er in the late 1950s (1) ushered in an exciting era o f research on the function of m elatonin and the pineal gland, which has become very intense over the past decade. O f primary importance for understanding the function o f melatonin is the signature feature o f its production and release into the general circulation: it is secreted primarily during the darkness in all m ammalian species (2), with there being very low levels o f melatonin in the circulation during the daytime. Thus, in humans high levels o f melatonin are present in the blood stream during the normal time of sleep (3) (Fig. 1). This correlation with the sleep-wake cycle coupled with two responses to exogenous melatonin have led to a great deal o f interest in recent years that melatonin may be involved in the regulation o f sleep, and that exogenous m elatonin and/or analogs o f melatonin may represent a new class o f hypnotics for the treatment o f insomnia. First, although controversial and contradictory in nature, a fairly extensive litera ture now exists on the hypnotic effects o f melatonin. Second, as discussed more fully in Chapter 7 (4), melatonin can have chronobiotic properties, meaning it can
Figure 1 Mean melatonin profiles (±SEM) over a 24-hr time period from eight normal adults (four men, four women) studied in dim light conditions (<200 lux). The dark bar represents the sleep period in darkness. (Van Cauter, unpublished results)
influence the phase and/or the period of the circadian clock regulating most if not all circadian (i.e. 24 hr) rhythms in mammals. Since the circadian clock plays a central role in the timing of sleep and wakefulness, any effects of melatonin on the clock would influence the timing of sleep under normal conditions as well as when sleep is occurring at abnormal times, as occurs during jet lag or in shift workers.
