The pineal gland in human beings: relevance to pediatrics.

Several facts suggest that the pineal gland must have a significant role in human beings: the presence of melatonin secretion from infancy to old age; a circadian secretory pattern similar to that found in animal species in which this gland has well-defined functions; its responsiveness to light; and the presence of melatonin receptors in the hypothalamus. Despite the importance of the pineal gland and melatonin in the reproductive activity of all nonprimate vertebrate species studied, the relationship of melatonin secretion to the activity of the hypothalamic-pituitary-gonadal axis in human beings remains presumptive. Some data suggest a possible pineal-reproductive connection throughout the human lifespan, but new research approaches are needed for a better definition of this connection during normal development and in disorders of the reproductive axis. In addition, recent studies that have applied strictly defined techniques to unravel the masking effects of various behavioral and environmental factors suggest that the pineal gland and melatonin have a fundamental role in the regulation of the human biologic clock. Melatonin concentrations in blood or urine may become a useful marker of the circadian rhythm in disorders of rhythms. Moreover, administration of melatonin in physiologic or pharmacologic doses may have an important application in suppression of the hypothalamic-pituitary-gonadal axis as a contraceptive, and in therapy for disorders of biologic rhythms. Among the latter, of particular interest to the pediatric population will be the potential application of melatonin treatment in establishing or reestablishing circadian rhythms in infants and children maintained for long periods under artificial light conditions, as encountered in intensive care units, and in the treatment of sleep and other rhythm disorders associated with developmental delay or blindness. Further research and approval by the U.S. Food and Drug Administration will be required before these applications will be available to the practicing pediatrician. The identification of melatonin receptors in the human hypothalamic fetal and adult tissues and the development of potent melatonin agonists and antagonists have paved the way for new research approaches that are needed to further investigate this intriguing, long-forgotten gland in human beings.