Physiology of the Pineal Gland and Melatonin

The scientific paper by Arendt et al., titled Physiology of the Pineal Gland and Melatonin, provides a detailed review of the pineal gland and its primary hormone, melatonin. The authors explore how melatonin is synthesized in response to environmental light-dark cycles and how it regulates sleep, circadian rhythms, seasonal changes, and various physiological functions such as metabolism, thermoregulation, reproduction, and aging. The paper also discusses how melatonin production can be disrupted by factors such as aging, neurological conditions, medications, and light exposure at night. By examining decades of research, the authors outline melatonin’s mechanisms of action, target receptors, and potential clinical applications, especially in sleep and mood disorders.

This scientific paper by Arendt et al. explores how the pineal gland—a small, central structure in the brain—plays a key role in producing melatonin, the hormone that helps regulate our internal biological clock. Often referred to as the body’s “darkness hormone,” melatonin is released at night and helps control our sleep-wake cycle, mood, and body temperature. The study also highlights melatonin’s broader roles in reproduction, metabolism, and aging. While the hormone has long been associated with sleep, this research shows it may influence many other systems in the body. Disruptions in melatonin production can occur due to aging, light exposure, medication, or injury, which may lead to circadian rhythm disorders or other health issues.

This paper is a review of existing scientific research on melatonin and the pineal gland. It draws on laboratory experiments, human clinical trials, observational studies, and genetic research. The authors use data from both animal and human studies to explain how melatonin is made, how it works in the body, and how its effects can be harnessed for health applications. The review also summarizes findings on melatonin-related disorders and its clinical use for sleep and mood regulation.

Melatonin is produced by pinealocytes in the pineal gland. Its release follows a daily cycle—rising after sunset, peaking in the middle of the night, and falling by morning. This rhythm is guided by light signals received by the eye and sent to the brain’s master clock, the suprachiasmatic nucleus (SCN). In darkness, nerve signals activate the enzyme AA-NAT, triggering melatonin production. The study explains that “NE is the trigger for the pinealocytes to produce melatonin by activating the transcription of the mRNA encoding the enzyme arylalkylamine N-acetyltransferase (AA-NAT).”

Melatonin is also made in other body parts like the skin, retina, and gut, but these don’t contribute much to blood levels. Notably, melatonin can also be made inside mitochondria, where it protects cells from stress and damage.

The SCN sets the rhythm for melatonin secretion and, in turn, melatonin feeds back to the SCN. This creates a feedback loop that keeps our sleep-wake cycle in sync with the environment. The study notes that “light exposure is the most important factor related to pineal gland function and melatonin secretion.” Even low levels of indoor light at night can suppress melatonin production and shift the circadian rhythm.

Blind people who lack light perception often have free-running rhythms and rely on melatonin supplements to stay aligned with the 24-hour day.

Melatonin is almost undetectable at birth but rises quickly in infancy and peaks in childhood. It starts to decline during adolescence and continues to decrease with age. By age 90, melatonin levels can be less than 20% of what they were in young adults. Factors like pineal gland calcification and reduced nerve input are thought to contribute to this decline.

Melatonin rhythms are also influenced by puberty, the menstrual cycle, and reproductive hormones. In some cases, higher melatonin levels are linked to delayed puberty or amenorrhea. However, the study points out that “a causal role of melatonin in pubertal development has not been described.”

Melatonin acts in the brain and throughout the body through MT1 and MT2 receptors, which help regulate sleep, reproductive hormones, and body temperature. It also crosses cell membranes easily, allowing it to act directly as an antioxidant. These dual actions allow melatonin to protect against cellular damage and possibly play a role in preventing aging.

The nighttime melatonin peak usually aligns with the lowest point in body temperature and greatest sleepiness. When taken during the day, melatonin can lower body temperature and increase drowsiness, especially in seated individuals. The study adds that melatonin “plays a role in circadian thermoregulation.”

Melatonin also helps regulate insulin sensitivity and fat metabolism. People who sleep less or have misaligned sleep-wake cycles may have higher risks of insulin resistance and type 2 diabetes. Some gene variants affecting melatonin receptors are also linked to lower beta-cell function.

Melatonin is a powerful antioxidant and may help protect against DNA damage, especially when exposure to harmful agents occurs at night. In animal models, rats given carcinogens at night had less DNA damage than those treated during the day. The study also notes that people exposed to light at night, such as shift workers, may have a higher risk of hormone-related cancers like breast cancer. This is thought to be due to melatonin suppression and resulting changes in estrogen production.

This scientific paper shows that melatonin is not just a “sleep hormone.” It is a central part of the body’s internal clock system, influencing sleep timing, seasonal patterns, hormone balance, metabolism, and even how cells handle stress. Its production depends heavily on light exposure, and disruptions in its rhythm are linked to health problems ranging from insomnia to diabetes and possibly cancer.

The authors emphasize that while melatonin supplements are widely used and generally safe, their timing and dosage must be personalized for each person. As more is learned, melatonin may become a key part of managing sleep disorders, neurodegenerative diseases, and age-related health concerns. Future research is needed to better understand its full range of effects and to develop guidelines for its safe and effective use.