Human melatonin in physiologic and diseased states: neural control of the rhythm

The human melatonin rhythm is endogenous with a surge of secretion entrained to the dark part of the cycle. Reports show consistent blunting or blockade of this nocturnal surge in the presence of sympathetic neurologic lesions and after administration of beta-adrenergic antagonists. However, there is remarkable resistance to elevation of daytime melatonin secretion by adrenergic agonists and by conditions of general sympathetic hyperactivity. Analysis of these and other reports together with results in lower animals allows insight into the control of the human melatonin rhythm. This rhythm is driven by a neural pathway to the pineal gland similar to that in animals and includes the sympathetic nervous system acting through a beta-adrenergic mechanism. Sympathetic control of the pineal is exerted independently of general sympathetic function, with sympathetic information partitioned separately for the pineal. The pineal is protected from humoral and exogenous adrenergic agents, in part by a nerve ending reuptake mechanism which has been demonstrated in rats and hamsters. Results in Syrian hamsters also suggest that sensitivity of the pineal to norepinephrine appears only at night. Melatonin production is an index, not of general sympathetic activity, but of the activity in a specific pathway and provides a stable humoral signal reflecting light/dark exposure. Observations of reduced melatonin values as a function of puberty, age, and depressive illness are not yet understood in the context of a unitary explanation of pineal function but indicate interesting frontiers in this field.