The Pharmacology of the Pineal Gland
Authors: K P Minneman, R J Wurtman
Journal: The Annual Review of Pharmacology and Toxicology (1976)

Only recently have a sufficient number of publications been available to legitimize a review of the pharmacology of the mammalian pineal organ. Two decades ago Kitay & Altschule reviewed the world literature on pineal physiology, which comprises several thousand papers, and concluded only that removal of the pineal, or administration of pineal extracts, somehow affected pigmentation in lower vertebrates and gonadal function in mammals (1). As the studies described below demonstrate, much more information is now available concerning the pharmacology of the pineal. This review subdivides present knowledge into two areas: (a) the effects on mammals of administering pineal extracts or pure synthetic or natural pineal constituents and (b) the effects of drugs and hormones on the pineal itself. As might be anticipated, the bulk of studies cited in both categories deals with the pineal hormone, melatonin. Melatonin was first isolated from bovine pineal extracts in 1958 by Lerner and his colleagues (2), who used as a marker the capacity of the hormone to aggregate the pigment granules in amphibian melanophores around the cell nucleus. Five years later, Wurtman et al (3) showed that melatonin affected a physiological function in mammals, that is, the size and secretion of the ovary, and subsequent studies have demonstrated that melatonin administration also modifies the growth, composition, and functional activities of numerous other organs. Only recently an assay was developed that allows quantification of the melatonin in human urine (4). The concentrations of the compound vary with a characteristic daily rhythm, peaking at night. The pineal's apparent role as the sole or major source of melatonin, the presence of melatonin in urine, and the demonstration that physiologic effects follow a pinealectomy or the administration of melatomin seem to justify labeling it a pineal hormone. Melatonin synthesis and pineal biosynthetic activity are generally controlled by the sympathetic nerves of this organ (5,6). Therefore, it should not be surprising that drugs known to modify the synthesis, release, or metabolism of norepinephrine in peripheral organs also affect pineal function. Melatonin is itself a derivative of another biogenic amine, serotonin, whose metabolism and actions are also affected by numerous drugs. Indeed, the pineal has often provided an apt tool for examining monoaminergic mechanisms for pharmacologists not specifically concerned with its particular functional properties.Literature on the pharmacology of the mammalan pineal gland is reviewed. The avilable data indicate that melatonin, a methoxyindole synthesized in and secreted from the pineal gland, is responsible for many of the biological functions attributed to the pineal. Considerable attention has been given to the effects of melatonin on the brain and consequent suppression of the aturation and functional activity of the gonads. A 24-hour rhythmicity of melatonin synthesis has been demonstrated, with greatest levels in human urine corresponding to hours of darkness. Drugs that enhance the interactions of norepinephrine with pineal beta-receptors stimulate melatonin synthesis, while beta-receptor blocking agents suppress melatonin synthesis. Certain peptides and other methoxyindoles may also be biologically active in the pineal gland.