The Pineal Gland and Melatonin

The pineal gland or epiphysis synthesizes and secretes melatonin, a structurally simple hormone that communicates information about environmental lighting to various parts of the body. Ultimately, melatonin has the ability to entrain biological rhythms and has important effects on reproductive function of many animals. The light-transducing ability of the pineal gland has led some to call the pineal the "third eye".

Anatomy of the Pineal Gland

The pineal gland is a small organ shaped like a pine cone (hence its name). It is located on the midline, attached to the posterior end of the roof of the third ventricle in the brain. The pineal varies in size among species; in humans it is roughly 1 cm in length, whereas in dogs it is only about 1 mm long. To observe the pineal, reflect the cerebral hemispheres laterally and look for a small grayish bump in front of the cerebellum.

How does the retina transmit information about light-dark exposure to the pineal gland? Light exposure to the retina is first relayed to the suprachiasmatic nucleus of the hypothalamus, an area of the brain well known to coordinate biological clock signals. Fibers from the hypothalamus descend to the spinal cord and ultimately project to the superior cervical ganglia, from which post-ganglionic neurons ascend back to the pineal gland. Thus, the pineal is similar to the adrenal medulla in the sense that it transduces signals from the sympathetic nervous system into a hormonal signal.

Melatonin: Synthesis, Secretion and Receptors

The precursor to melatonin is serotonin, a neurotransmitter that itself is derived from the amino acid tryptophan. Within the pineal gland, serotonin is acetylated and then methylated to yield melatonin.

The mechanism behind this pattern of secretion during the dark cycle is that activity of the rate-limiting enzyme in melatonin synthesis - serotonin N-acetyltransferase (NAT) - is low during daylight and peaks during the dark phase. In some species, circadian changes in NAT activity are tightly correlated with transcription of the NAT messenger RNA, while in other species, post-transcriptional regulation of NAT activity is responsible. Activity of the other enzyme involved in synthesis of melatonin from serotonin - the methyltransferase - does not show regulation by pattern of light exposure.

Two melatonin receptors have been identified from mammals (designated Mel1A and Mel1B) that are differentially expressed in different tissues and probably participate in implementing differing biologic effects. These are G protein-coupled cell surface receptors. The highest density of receptors has been found in the suprachiasmatic nucleus of the hypothalamus, the anterior pituitary (predominantly pars tuberalis) and the retina. Receptors are also found in several other areas of the brain.