The Melatonin Hypothesis
Melatonin (N-acetyl-5-methoxytrptamine) is a hormone produced nocturnally in the pineal gland. Its production is triggered by a signal from the eye indicating that light has fallen below ~200 lux. This trigger does not involve the visual system rather recently discovered ganglion cells in the eye (Berson et al. 2002; Hattar et al. 2002). Melatonin is a powerful antioxidant and radical scavenger whose mechanisms of action, some of which are cell receptor mediated, has been extensively researched. As an antioxidant, melatonin acts as a natural anti-cancer agent but it is also known to regulate seasonal breeding in animals and reduced melatonin is associated with depression. The decline in production of melatonin in the aged is associated with the onset of neurodegenerative diseases (see review in Reiter 1998).Unlike other antioxidants, such as vitamins C and E and glutathione, melatonin enters cells and is able to act directly on DNA. Indeed, the concentration of melatonin in cells, tissues and organs is markedly non-uniform (see Editorial by Reiter 2003). As a result, the so-called normal physiological concentrations of melatonin need to be carefully defined. For example, melatonin concentrations in bile and in the cerebrospinal fluid of the third ventricle are orders of magnitude higher than in the blood.
The nocturnal production of pineal melatonin can be completely suppressed by exposure to light-at-night (LAN). Nowadays, compared to our forefathers, man is exposed to far more LAN, from street and indoor lighting, with a corresponding reduction in the total amount of nocturnal melatonin produced. The so-called melatonin hypothesis (Stevens 1987), postulates that the increased risk in breast cancer in recent decades in industrialised countries results in part from increased exposure to LAN. Strong support for this hypothesis comes from the increased risk of breast cancer in nightshift workers (Swerdlow 2003) and the fact that such workers who go on to contract breast cancer produce lower nocturnal melatonin (Schernhammer & Hankinson 2005). Further support comes from the recent observation that normal physiological concentrations of nocturnal melatonin in women