I\'m reading a booklet on melatonin published in 1996, titled \"Melatonin and th
ID: 31047 • Letter: I
Question
I'm reading a booklet on melatonin published in 1996, titled "Melatonin and the Biological Clock". This particular paragraph caught my attention and I would like to better understand what it means:
The requirement of intact beta-receptor function for melatonin synthesis, and the stimulatory effect of norepinephrine on melatonin synthesis and release, point up a theoretic relationship of melatonin to depression.
I've been looking at the biosynthesis of norepinephrine and tryptophan metabolism and do not see how the two cycles are connected. Is there a connection between the norepinephrine system and the melatonin synthesis in humans?
Explanation / Answer
Melatonin is not only synthesized by the pineal gland but also in many other organs and tissues of the body, particularly by lymphoid organs such as the bone marrow, thymus and lymphocytes. Melatonin participates in various functions of the body, among which its immunomodulatory role has assumed considerable significance in recent years. Melatonin has been shown to be involved in the regulation of both cellular and humoral immunity. Melatonin not only stimulates the production of natural killer cells, monocytes and leukocytes, but also alters the balance of T helper (Th)-1 and Th-2 cells mainly towards Th-1 responses and increas- es the production of relevant cytokines such as interleukin (IL)-2, IL-6, IL-12 and interferon-?. The regulatory function of melatonin on immune mechanisms is seasonally dependent. This fact may in part account for the cyclic pattern of symptom expression shown by certain infectious diseases, which become more pronounced at particular times of the year. Moreover, melatonin-induced seasonal changes in immune function have also been implicated in the pathogenesis of seasonal affective disorder and rheumatoid arthritis.
Is there a connection between the norepinephrine system and the melatonin synthesis in humans?
In vertebrates, the link between norepinephrine (NE) and melatonin lies in the regulation of the melatonin biosynthetic pathway.
Arylalkamine N-acetyltransferase (AANAT) is an enzyme in the biosynthetic pathway for melatonin, and controls the diurnal rhythm of melatonin production in the pineal gland. NE is released as a neurotransmitter by neurons innervating the pineal gland, and which themselves are regulated by the circadian pacemaker of the hypothalamus. One of the effects of NE on the pineal gland is to elevate the transcription of the AANAT gene via adrenoreceptors and cAMP levels.