Perspectives in Biology and Medicine

MELATONIN: PATHWAY FROM OBSCURE MOLECULE TO INTERNATIONAL FAME FRED W. TUREK* Introduction There are few people who follow the news in the United States who have not heard of the hormone melatonin. In European and Asian countries melatonin has also been in the news. Many people are now taking melatonin for everything from insomnia, heart disease, cancer, AIDS, and sexual impotency, as well as to try and slow down the aging process. In the United States, melatonin is sold widely without prescription in vitamin and dietary supplement stores, as well as through many drug stores and supermarkets. The discussion of the effects of melatonin is frequently a major topic on the radio and television news. Melatonin has been featured in national magazines, and books on melatonin have made it to "bestseller" status. Yet, just a few years ago the general public was unaware of even the existence of melatonin, and any discussions of the effects of melatonin were confined to a few investigators attempting to discover the function of this hormone. This paper does not attempt to review the diverse literature on the effects of melatonin; the reader is referred to two recent books for scholarly treatment of this subject [1, 2]. Instead, this review provides a brief history of how melatonin rose from being an obscure molecule to achieve national and even international celebrity status. It is a story that involves not only scientific discovery, but also sensational stories in the media, the profit motive in a capitalistic society, and how the sale of drugs is regulated—or in melatonin's case, not regulated—in the United States. The roots of what has been called "melatonin madness" [3] lie in a rich history of diverse studies that have implicated the pineal gland and melatonin in the regulation of daily and seasonal biological rhythms in a wide range ofvertebrate species. As noted below, the photoreceptive prop- *Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.© 1997 by The University of Chicago. All rights reserved. 0031-5982/97/4101-1037$01.00 Fred W. Turek ¦ Melatonin: From Obscurity to Fame erties of pineal cells made it a candidate for mediating the effects of the light-dark cycle on daily and seasonal rhythms. Of particular importance was the discovery of melatonin in the late 1950s [4], and the finding that in almost all vertebrate species, the pineal gland synthesizes and releases melatonin into the general circulation in high amounts during the nighttime , and in low amounts during the day [I]. This characteristic of pineal melatonin meant it could at least in theory provide the organism with two important pieces of information about the 24-hour day. First, it could provide other parts of the organism with information as to the time of day, enabling the organism to adapt or change its biochemistry, physiology, and behavior in an appropriate manner to meet the demands of the changing environment over each 24-hour period. Second, melatonin could also function as a "calendar," informing the rest of the organism about the length of the night (or day), since during the long nights (in winter, for example) melatonin is produced for a longer period of time than during the short nights (in summer, for example). In order to provide a perspective on the role of melatonin in the control of daily and seasonal rhythms, it is first necessary to briefly review the nature of these biological rhythms. Daily and Seasonal Rhythms Even when we stay in one place, the surrounding biological and physical environment changes dramatically with time. On the short-term basis, we experience the never-ending daily cycle of light and dark due to the rotation of the earth on its axis. Except for organisms living deep in the oceans or underground, most living organisms on earth have had to adapt to daily changes in their environment. Indeed, the vast majority of organisms on earth are now known to contain a daily or "biological clock." This clock is normally synchronized or entrained to the daily cycle of light and dark such that the period of the endogenous clock and the rhythms under its control exactly match the 24-hour period of the earth...