Pinealocyte

Type 1 pinealocytes are also known as light pinealocytes because they stain at a low density when viewed under a light microscope and appear lighter to the human eye. These Type 1 cells have been identified through research to have a round or oval shape and a diameter ranging from 7–11 micrometers.[6] Type 1 pinealocytes are typically more numerous in both children and adults than Type 2 pinealocytes.[6] They are also considered to be the more active cell because of the presence of certain cellular contents, including a high concentration of mitochondria.[7] Another finding consistent with Type 1 pinealocytes is the increase in the amount of lysosomes and dense granules present in the cells as the age of the organism increases, possibly indicating the importance of autophagocytosis in these cells.[6] Research has also shown that Type 1 pinealocytes contain the neurotransmitter serotonin, which later is converted to melatonin, the main hormone secreted by the pineal gland.[8]

Type 2 pinealocytes are also known as dark pinealocytes because they stain at a high density when viewed under a light microscope and appear darker to the human eye. As indicated by research and microscopy, they are round, oval, or elongated cells with a diameter of about 7–11.2 micrometers.[6] The nucleus of a Type 2 pinealocyte contains many infoldings which contain large amounts of rough endoplasmic reticulum and ribosomes.[6] An abundance of cilia and centrioles has also been found in these Type 2 cells of the pineal gland.[7] Unique to the Type 2 is the presence of vacuoles containing 2 layers of membrane.[7] As Type 1 cells contain serotonin, Type 2 cells contain melatonin and are thought to have similar characteristics as endocrine and neuronal cells.[8]

Regulation of melatonin synthesis is important to melatonin’s main function in circadian rhythms. The main molecular control mechanism that exists for melatonin secretion in vertebrates is the enzyme AANAT (arylalkylamine N-acetyltransferase). The expression of the AANAT gene is controlled by the transcription factor pCREB, and this is evident when cells treated with epithalone, a peptide which affects pCREB transcription, have a resulting increase in melatonin synthesis.[8] AANAT is activated through a protein kinase A system in which cyclic AMP (cAMP) is involved.[4] The activation of AANAT leads to an increase in melatonin production.[4] Though there are some differences specific to certain species of vertebrates, the effect of cAMP on AANAT and AANAT on melatonin synthesis remains fairly consistent.[4]

Melatonin synthesis is also regulated by the nervous system. Nerve fibers in the retinohypothalamic tract connect the retina to the suprachiasmatic nucleus (SCN). The SCN stimulates the release of norepinephrine from sympathetic nerve fibers from the superior cervical ganglia that synapse with the pinealocytes.[1][4] Norepinephrine causes the production of melatonin in the pinealocytes by stimulating the production of cAMP. Because the release of norepinephrine from the nerve fibers occurs at night, this system of regulation maintains the body’s circadian rhythms.[1]

Pinealocytes synthesize the hormone melatonin by first converting the amino acid tryptophan to serotonin. The serotonin is then acetylated by the AANAT enzyme and converted into N-acetylserotonin. N-acetylserotonin is converted into melatonin by the enzyme hydroxyindole O-methyltransferase (HIOMT), also known as acetylserotonin O-methyltransferase (ASMT).[1] Activity of these enzymes is high during the night and regulated by the mechanisms previously discussed involving norepinephrine.[1]

Synthesis of Melatonin