THE PINEAL GLAND AND CIRCADIAN RHYTHM
There are two types of glands within the endocrine system: exocrine glands and endocrine glands. Exocrine glands are chiefly responsible for the secretion of nonhormonal substances such as sweat and saliva. Secretion ducts are responsible for the release of the nonhormonal substances to the membrane surface. In contrast, endocrine glands are ductless glands that function in the production of hormones and secrete directly into the bloodstream. The endocrine glands present in the human body are pituitary, thyroid, parathyroid, adrenal, and pineal glands. Much is known about the functionality endocrine glands. However, the pineal gland is deemed one of the most mysterious glands in human physiology for its overall function and intrinsic physiological necessity.
The pineal gland is a relatively small gland in comparison to the other glands in the endocrine family and is located posterior to the thalamus, superior to the midbrain, and attached to the anterior pole of the brain’s third ventricle. The identification of the pineal gland dates back to 130-200 AD where Galen of Pergamon first characterizes it as a lymph gland. He named the gland “‘konareion’ (Latin ‘conarium’) for its pine cone shape”  and then “was subsequently named ‘glandula pinealis,’ hence ‘pineal’” . The pineal gland is also thought to be “named after a French psychologist, Philippe Pinel (1745-1826), who first described the gland in the human brain” . Regardless of the pineal gland’s origin, the primary function remains the same: the production and secretion of melatonin.
“The best characterized function of the pineal gland is the nocturnally elevated synthesis of the hormone melatonin, which provides the body with the signal of the duration of the night period” . Melatonin secretion is conducted by photoreceptive pinealocytes. The pinealocytes function on a circadian rhythm, regulation sleep-wake cycles in most mammalian species. The rhythm expressed is “one of the few rhythms that is the same in nocturnal and diurnal mammals” . During the day, the pineal gland secretes low levels of melatonin. As the day progresses, melatonin levels begin to increase, reaching its peak midway through the night. Melatonin level will then decline until it reaches daytime levels just before dawn. It is because of the circadian characteristic that the pineal gland is deemed, “‘third eye’ of lower vertebrates, whose rhythmic synthesis of melatonin reflects external time” .
The origin of melatonin synthesis stems from the neurotransmitter serotonin. The process is conducted in two phases where serotonin is “N-acetylated by the enzyme, arylalkylamine N-acetyltransferase (NAT), and N-acetylserotonin is converted to melatonin by the enzyme, hydroxyindole-O-methyltransferase” . NAT regulation is the driving force of the circadian rhythm; low NAT activity results in low melatonin production and vice versa. As in all circadian patterns in humans, the clock requires entrainment to prevent free running. Therefore, a phasing factor or zeitgeber will be used to entrain the rhythm. It the case of melatonin regulation, the optic chiasm serves as the zeitgeber. “No pathways beyond the chiasm are necessary for entrainment of the NAT, and presumably the melatonin rhythm” . The pinealocytes in mammals are responsible for the suprachiasmatic-nuclei-driven neuroendocrine transducers  that inform the brain of the onset of darkness, enabling circadian control.
The limits of pineal gland function have yet to be discovered. It is known that, like all glands in the endocrine system, the pineal gland has a relationship with the nervous system with evidence of “peripheral sympathetic and parasympathetic fibers, as well as fibers originating in the central nervous system” . Additionally, melatonin studies have begun to uncover homeostatic malfunctions. Further knowledge has been obtained on the circadian rhythm effects of jet lag, blindness, and sleep patterns. The science behind melatonin production and synthesis has also provided breakthroughs in the advancements in developmental diseases such as Smith–Magenis mental retardation syndrome . The pineal gland is vital to human physiology. It’s characteristics and functions make it unique in comparison to other glands within the endocrine system. Deciphering the depth of this multi-dimensional wonder is critical to understanding the unsolved mystery of the “third eye”.
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