What does melatonin do?

Melatonin has two main types of receptor called ML1 and ML2 of high and low affinity respectively. Receptors have been found in a wide range of tissues including the brain (e.g. the suprachiasmatic nucleus and the hypothalamus), the pituitary gland, blood vessels, the adrenal glands, ovaries and testes. In addition it is thought to act on specific intracellular molecules (such as calmodulin, a protein in cells that alters intracellular calcium levels).

The precise functions of melatonin have not been identified but some actions include:

• Sleep and Circadian rhythms - administration of melatonin acts to increase sleepiness, the duration of sleep and the quality of sleep. In addition, depending on when it is given, it also acts to shift the phase of the circadian rhythms of the body including daily temperature changes, hormone levels and electrolyte levels (blood levels of ions such as calcium, sodium, potassium etc.)
• Cardiovascular effects - melatonin administration at pharmacological doses (higher than the levels seen in normal physiology) causes a drop in body temperature, presumably by affecting blood vessel diameters (dilation of blood vessels allows heat loss) and/or hypothalamic temperature regulation centres.
• Sexual Maturation - it has been suggested that melatonin exerts and inhibitory effect on the hypothalamopituitary-gonadal axis. That is to say it decreases the function of the gonads (the testes and the ovaries) by decreasing the stimulation of these organs by the brain. This has been used to account for phenomena such as lower sex hormone levels and decreased conception rates in the winter as opposed to the summer in populations living in the Arctic. Other anecdotal evidence includes case reports of precocious puberty (early sexual development) in children who have reduced function of the pineal gland, for example, due to destruction by tumours. The suggestion is that with melatonin removed, the brain can stimulate the gonads more readily promoting early sexual development. Related research has suggested that women with amenorrhoea (absence of periods) due to reduced stimulation of the ovaries by hormones from the brain (hypogonadotropic hypogonadism) may have elevated levels of melatonin that is inhibiting normal function. However, all this research is in its infancy and much more work is needed here.
• Immune modulation - melatonin seems to cause increased activity of immune cells called T cells (specifically CD4 cells). It also causes the production and release of chemicals such as interleukin 4 (IL-4) which are very important to the immune system. How this is involved in normal physiological function is not known.
  
  Cancer - melatonin may have protective effects against tumour growth, particularly ovarian, testicular and breast cancer, cancers promoted by high levels of certain sex hormones. Hypotheses as to how this work include an inhibitory effect on cell division, activation of the immune system against the tumour cells and protection of cells against DNA damage by oxidants and free radicals (see 'antioxidant properties'). It also appears the melatonin makes chemotherapy and radiotherapy regimes more tolerable, perhaps by preventing excessive damage to blood cells that often results.
• Antioxidant properties - melatonin, at doses much higher than would normally be found in people, has been shown to protect cells from damage by oxidants such as free radicals. Free radicals can damage essential molecules in the cell such as DNA (the building block of the genes). This can prevent gene mutations that can lead to cancer.