ABSTRACT

Discovery of an active substance in any component of a living system has never been so exciting as what happened with the isolation, puri£cation, and characterization of an indole compound from extracts of the pineal gland, which has long been considered as a functional relic of the brain [1]. The credit of such breakthrough research goes to a group led by an American dermatologist, Dr. Aaron Bunsen Lerner, in the Yale University School of Medicine, who extracted only a few milligrams of N-acetyl-5-methoxy-serotonin from more than 100,000 cattle pineal glands nearly 53 years ago [2,3]. They named this puri£ed pineal substance melatonin (MEL) in recognition of an initial observation that treatment with crude acetone extract of bovine pineal glands to Rana pipens tadpole caused a pronounced lightening (blanching) of their skins (i.e., melanophore-contracting hormone; Greek: μελαζ = black; τονζ = tension, in the sense of contraction), resulting in clear visibility of the larger viscera through the dorsal body wall [4]. Nevertheless, the functional implication of pineal has a history way back to the 19th century, when Huebner [5] reported for the £rst time that tumor of the human pineal altered pubertal development, indicating a possible role of some factor(s) of pineal origin in in—uencing reproductive functions. This observation led many scientists in the £rst half of the 20th century to experimentally examine the association of the pineal with the reproductive status in a variety of animal species with limited compelling evidences [6] (Table 1.1).