Role of Melatonin in Circadian Rhythm

Melatonin regulates the wake-sleep cycle by causing drowsiness and lowering body temperature, but which specific chemical pathways lead to this drowsiness?

This is a quite complicated question, as melatonin has quite a range of effects on the cells. First, melatonin binds to three different melatonin receptors, which are found in a wide variety of tissues or organs including brain and retina, cardiovascular system, liver and gallbladder, intestine, kidney, immune cells, adipocytes, prostate and breast epithelial cells, ovary/granulosa cells, myometrium, and skin.

Two of the receptors a G-protein coupled receptors (GPCR), the MT1 and MT2 receptors. The third is a quinone reductase called QR2.

For more details, see this papers:

The role of melatonin is pretty broad, see the figure (from this article:"Melatonin: Nature's most versatile biological signal?")

The receptors transport the outside chemical signal (the melatonin) to the inside and activate (or repress) a number of different signal transduction pathways. See the figure below (taken from Qiagen):

This includes MAP-Kinase pathways, proteinkinase C, IP3, adenyl cyclase and so on. This is quite complicated and I recommend reading some of the following articles if you are interested in a deeper insight. Finally these signals are transmitted into the nucleus and result in a changed gene regulation/expression.

From wikipedia article on melatonin receptors (with some modifications) :

In mammals, melatonin receptors, which are G protein coupled receptors, are found in the brain and some peripheral organs. However, there is considerable variation in the density and location of MT receptor expression between species.


In humans, The MT1 subtype is expressed in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus… This is indicative of its role in circadian and reproductive function.


The MT2 subtype is expressed in the retina. MT2 receptor mRNA has not been detected by in situ hybridization in the rat suprachiasmatic nucleo or pars tubealis. This receptor may have a role in light dependent functions.