Involvement of Calcium in Pineal Gland Function

Abstract

The pineal gland functions as a neurohumoral transducer, accepting photic information from the retinae and converting this neural message into chemical mediators, the best documented of which is melatonin (N-acetyl-5-methoxytryptamine) (1). The onset of darkness causes information to travel from the suprachiasmatic nuclei of the hypothalamus via the superior cervical ganglia to postganglionic sympathetic nerves that end in the pineal, where they release norepinephrine. The resultant stimulation of β-adrenergic receptors, possibly augmented by α-adrenergic stimulation, leads to an increased activity of N-acetyltransferase (NAT) (2), the rate-limiting enzyme involved in synthesis of melatonin (3). Serotonin, derived from dietary tryptophan taken up by pinealocytes from the blood, is N-acetylated by NAT, which is subsequently O-methylated by hydroxyindole-O-methyltransferase (HIOMT) to form melatonin, which is then released into the general circulation. Being a small lipophilic molecule, melatonin is generally considered to be released rapidly and passively following synthesis, although there is some evidence that short-term storage of melatonin by the pineal gland might occur (4). Melatonin's lipophilicity also ensures that it distributes widely to target tissues, which, therefore, receive photoperiodic information and can subsequently act with appropriate physiological responses (5).

The multiplicity of extracellular and intracellular events that interact to produce the melatonin message are not fully understood, although certain aspects have been reasonably well characterized. For example, it is well-known that β-adrenergic stimulation leads to activation of adenylate cyclase, and that the resultant increase in CAMP stimulates mRNA synthesis, leading to increased NAT activity (3). The α-adrenergic augmentation of this process results from activation of protein kinase C. A number of stimulatory/regulatory processes involved in melatonin production have been associated with calcium, and the following discussion serves to review current understanding of the relationship between calcium and pineal gland function.