Fig. 7

Melatonin’s synthesis and release. Melatonin is a dark hormone where its synthesis and release from the pineal gland depend on the the the dark/light signal it receives from the “central biological clock”, the suprachiasmatic nucleus (SCN) in the hypothalamus. The SCN receives light information through the retinal-hypothalamic tract from retinal ganglionic cells and then sends adrenergic sympathetic fibers to the pineal gland after synapsing in the paraventricular nucleus (PVN) of the hypothalamus and the superior cervical ganglia (SCG). The post-ganglionic sympathetic fibers releases noreadrenaline (NE), which activates the pinealocyte ß and α1 adrenergic receptors. The activation of ß receptors activates adenyl cyclase (AC), which increases cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). The activation of α1-adrenergic receptors activates phospholipase C (PLC) which acts on Phosphatidylinositol 4,5-bisphosphate (PIP2) to form 1,2-diacylglycerol (DAG) and inositol trisphosphate (IP3) and increases intracellular Ca⁺² and protein kinase C (PKC). The expression of PKA and PKC promotes the transcription of melatonin-forming enzymes. Melatonin is formed in pinealocytes from tryptophan. Tryptophan is turned into hydroxy-tryptophan (5-HTP) by tryptophan hydroxylase. 5-HTP is turned into serotonin (5-HT) by decarboxylase. 5-HT is converted into N-acetylserotonin by Serotonin-N-acetyl transferase (SNAT). Finally, N-acetylserotonin is converted into melatonin by hydroxyindole-O-methyltransferase (HIOMT)