Pineal gland and melatonin

Pineal gland and melatonin

The pineal gland or pineal gland synthesizes and releases melatonin, a structurally simple hormone that transmits information about environmental lighting to various parts of the body. Ultimately, melatonin has the ability to enthrall biological rhythms and has an important effect on the reproductive function of many animals. The easily transducing ability of the pineal gland caused some to call the pineal "third eye".

Anatomy of the pineal gland

The pineal gland is a small organ, similar to a pine cone (hence the name). It is located on the midline attached to the posterior end of the roof of the third ventricle in the brain. The pineal variety varies by species; in humans, it is about 1 cm in length, while in dogs it is only about 1 mm long. To observe the pineal muscle, reflect the cerebral hemispheres in the transverse direction and find a small grayish protrusion in front of the cerebellum. The pictures below show the horse's pineal gland in relation to the brain.

Histologically, the pineal structure consists of "pineal" and glial cells. In older animals, the pineal gland often contains calcium deposits (“brainwash”).

How does the retina transmit to the pineal gland? The light impact of the retina is first transmitted to the suprachiasmatic nucleus of the hypothalamus, a region of the brain well known for coordinating the signals of a biological clock. The fibers of the hypothalamus descend to the spinal cord and are ultimately projected into the superior cervical ganglia, of which, after the ganglion neurons, ascend to the pineal gland. Thus, the pineal membrane is similar to the adrenal brain in the sense that it transforms signals from the sympathetic nervous system into a hormonal signal.

Melatonin: synthesis, secretion and receptors

Melatonin's precursor is serotonin, a neurotransmitter, which itself is derived from tryptophan amino acid. Inside the pineal gland, serotonin is acetylated and then methylated to produce melatonin.

The synthesis and secretion of melatonin strongly depends on the effect of light on the eyes. The observed fundamental pattern is that serum melatonin concentrations are low during the daytime and increase to a maximum during darkness.

Pineal gland and melatonin

Examples of circadian rhythm in melatonin secretion in humans are depicted in the figure on the right (adapted from Vaughn, et al., J Clin Endo Metab 42: 752, 1976). Dark gray bands represent the night, and serum melatonin levels are shown for two individuals (yellow or light blue). Please note that the level of melatonin in the blood is almost not detected in the daytime, but increases dramatically during darkness. Very similar patterns are found in other species. The duration of melatonin secretion every day is directly proportional to the duration of the night.

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

Two melatonin receptors have been identified in mammals (designated Mel1A and Mel1B), which are differentially expressed in different tissues and are likely to be involved in the implementation of various biological effects. These are cell surface receptors associated with protein G. The highest density of receptors was found in the suprachiasmatic nucleus of the hypothalamus, the anterior pituitary (mainly pars tuberalis) and the retina. Receptors are also found in several other areas of the brain.

The biological effects of melatonin

Melatonin has important effects in integrating the photoperiod and influencing circadian rhythms. Consequently, it is reported that it has a significant effect on reproduction, sleep cycles and other phenomena indicating a circadian rhythm.

Reproductive Effects

Seasonal changes in the length of the day have an enormous effect on reproduction in many species, and melatonin is a key player in controlling such events. In temperate climates, animals such as hamsters, horses and sheep have a different breeding season. During the non-breeding season, the gonads become inactive (for example, men cannot produce sperm in any quantity), but as the breeding season approaches, the gonads should be rejuvenated. A photoperiod — day length versus night — is the most important signal that allows animals to determine in which season it is. As you may have guessed, the pineal gland is able to measure the length of the day and regulate melatonin secretion accordingly. A hamster without a pineal gland or with a lesion that prevents it from receiving photonicity cannot prepare for the breeding season.

Pineal gland and melatonin

The effect of melatonin on reproductive systems can be summarized by saying that it is antigonotropic. In other words, melatonin inhibits the secretion of gonadotropic hormones luteinizing hormone and follicle-stimulating hormone from the anterior pituitary gland. Most of this inhibitory effect is due to the inhibition of gonadotropin-releasing hormone from the hypothalamus, which is necessary for the secretion of anterior pituitary hormones.

It is a practical application. For example, a sheep can be induced to have two breeding seasons by treatment with melatonin.

Effect on sleep and activity

Melatonin is probably not the main regulator of normal sleep, but it certainly has some effect. One of the topics that aroused great interest is the use of only melatonin or in combination with phototherapy for the treatment of sleep disorders. There is some indication that melatonin levels are lower in elderly insomnia compared with age-related insomnia, and melatonin therapy in such cases appears modestly useful for correcting the problem.

Another sleep disorder is observed in shift workers, who often find it difficult to adapt to work at night and sleep during the day. The usefulness of melatonin therapy to alleviate this problem is ambiguous and, apparently, not as effective as phototherapy. Another condition associated with circadian rhythm disturbances is jet lag. In this case, it has been repeatedly demonstrated that taking melatonin near the target destination sleep time can alleviate the symptoms; this has the greatest positive effect when it is predicted that the liner’s delay will be the worst (for example, crossing many time zones).

It has been shown that in various species, including humans, a decrease in the activity of the musculoskeletal system, inducing fatigue and a decrease in body temperature, especially at high doses. Effects on body temperature can play a significant role in melatonin's ability to enthrall sleep cycles, as in patients with jet lag.

Other effects of melatonin

One of the first experiments conducted to determine the function of the pineal gland, extracts of the pineal glands in cattle was added to water containing tadpoles. Interestingly, tadpoles reacted by becoming very light or almost transparent due to changes in the distribution of melanin pigments. Although such skin effects of melatonin appear in a variety of “lower species”, the hormone does not have this effect in mammals or birds.

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