Melatonin- Not the Sleep Hormone

The one thing everyone knows about melatonin is that it is the “sleep hormone”.  This is wrong.  Rather, melatonin is a  darkness hormone that tells the body time of day and season of year.  It is released (primarily) from the pineal gland when sensors in the eye detect diminishing light or darkness.  In humans, this leads to a series of functions, including causing us to want to sleep and to stay asleep.  However, melatonin is evolutionarily one of the most ancient hormones and is found in nearly every animal and even plant species, and it has different effects in different species.  So, in nocturnal animals, for example, it is the “wake up” hormone.  In seasonal breeding animals (like horses) it is the sleep hormone and also the “time to reproduce” or “time not to reproduce” hormone.  This is because long summer days mean less exposure to darkness and, therefore, less melatonin production, and short winter days result in more and longer melatonin production.

Moreover, melatonin has a broad range of effects throughout the body besides sleep/wake or breeding/non-breeding cycles.  Cells having melatonin receptors (and thus that are capable of using melatonin) are found throughout the body, including heavy concentrations in the central nervous system, retina, blood vessels, mammary glands, GI tract, kidneys, testes, ovaries, prostate and, in non-human mammals, pituitary and adrenal glands.  Melatonin is used in treating Cushing’s disease, sleep disorders, seasonal and other depression, high blood pressure, glaucoma, hormone disorders and many other conditions. In addition, melatonin production decreases as we age and in conjunction with certain diseases.  Thus, melatonin supplementation is necessary in older people and pets and those with certain conditions such as Alzheimer’s disease and cardiovascular disease.  Decreases in melatonin levels have been linked to insomnia and a higher prevalence of cancer. 

What are some of the uses and benefits of melatonin?

Melatonin is a powerful antioxidant, and this alone probably accounts for many of melatonin’s health benefits.  It counters oxidative stress throughout the body, negating a major cause of disease, especially in older people and non-human animals.

The eye in particular is a heavy user of melatonin.  In fact, melatonin is so important to eye functions, that the eye produces its own melatonin (the rest of the body depends on the pineal gland for its melatonin) and contains many cells that take up melatonin.  Among other functions in the eye, it is an important hormone for regulating the growth and remodeling of the sclera (white part) of the eye and thus impacts eye size and refraction.  Melatonin also regulates intraocular eye pressure and thus can aid in the treatment of glaucoma.

The central nervous system is another heavy user of melatonin.  Melatonin has been shown to enhance the firing rate of neurons in the hippocampus and to enhance memory consolidation.  In one study, melatonin supplementation was as effective as a 2-hour mid-day nap (!) in enhancing performance in verbal association tasks.  Other studies have shown improvements in cognitive function in Alzheimer’s patients and those with mild cognitive impairment.  Furthermore, melatonin is useful in reducing some symptoms of Parkinson’s disease and in improving mood in those who suffer from winter or seasonal depression.

Those with coronary disease and those who suffer from high blood pressure (of the type that does not decline at night) have significantly lower nightly melatonin secretion and thus may require supplemental melatonin to maintain normal levels.  Melatonin has also been shown to lower blood pressure.  In one study, just 1 mg of melatonin taken orally was enough to reduce mean blood pressure by about 6 mmHg.

Why is melatonin prescribed for the treatment of Cushing’s syndrome?

There are two main mechanisms that make melatonin (in combination with lignans) an effective treatment for Cushing’s syndrome.  The first is its powerful antioxidant properties.  The persistent, elevated cortisol and other hormone levels in Cushing’s animals lead to oxidative stress throughout the body.  Antioxidants like melatonin can reduce or eliminate further oxidative-stress-induced damage.  The second is its direct impact on cortisol and related hormone levels.  Melatonin and cortisol levels are negatively correlated in diurnal (daytime-active) species--whereas melatonin levels peak at onset of darkness, cortisol levels peak just before the onset of light (and may have other peaks during the day, depending on the species).  Although cortisol levels are mainly controlled by their own clock system, melatonin itself also plays a role in regulating cortisol levels.  A study published in 2011 showed, for the first time, that melatonin directly inhibits the production of cortisol and other adrenal hormones in human adrenal glands.  (The human adrenal gland is often used as a model for the dog adrenal gland.)  In particular, that study showed significantly lower cortisol, progesterone and 3-beta-hydroxysterone (an enzyme essential for the generation of virtually all steroid hormones including cortisol, testosterone and estrogen) production.  

Melatonin is also intricately connected with reproduction and has been shown to decrease sex hormone secretion and modulate aromatase (an enzyme that leads to estrogen production) activity in various cell types.  Cushing’s animals (especially those with atypical Cushing’s syndrome) often have elevated levels of estrogen and other sex hormones. 


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Campino, Carmen & Valenzuela, Francisco & Torres-Farfan, Claudia & Reynolds, H. & Abarzua-Catalan, Lorena & Urzua, Eugenio & Trucco, Cristian & Guzman, Stephanie & Valenzuela, Guillermo & Seron-Ferre, Maria. (2011). Melatonin Exerts Direct Inhibitory Actions on ACTH Responses in the Human Adrenal Gland. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 43. 337-42. 10.1055/s-0031-1271693. 

Russel J. Reiter, Dun-Xian Tan, Lucien C. Manchester, Sergio D. Paredes, Juan C. Mayo, Rosa M. Sainz, Melatonin and Reproduction Revisited, Biology of Reproduction, Volume 81, Issue 3, 1 September 2009, Pages 445–456,

Kellie A. Fecteau, Hugo Eiler, and Jack W. Oliver (2011). Effect of combined lignan phytoestrogen and melatonin treatment on secretion of steroid hormones by adrenal carcinoma cells.  American Journal of Veterinary Research, May 2011, Vol. 72, No. 5 , Pages 675-680 (