Melatonin in humans-where we are 40 years after its discovery

Although the pineal gland was well known for more than 2000 years and has been documented since Galen (130-200 AD), for many centuries different theories concerning its function were presented. The organ was believed to be a sphincter (ancient Greeks), the point at which the soul preeminently controls the body (Descartes, 1596-1650), a rudimentary organ (up to the 19th century), and a gland having endocrine function. Endocrine function of the pineal was postulated already at the end of 19th century and the beginning of the 20th century with the notion of antigonadotropic pineal influence, and the functional cooperation between the pineal and hypothalamo-hypophysial axis, but no secretory substance responsible for the gland function was known. In 1958 Lerner and coworkers succeeded in isolating from bovine pineal glands the compound termed melatonin because of its blanching effect on melanophores. This discovery constituted the milestone for further pineal research. Since then the knowledge of the structure and function of the pineal gland has tremendously increased, especially during the last two decades. However, it should be stressed that many problems in pineal research still must be solved. In this paper, the recent knowledge on the role of melatonin in humans is briefly presented.