The FIRSTS: Melatonin (1958)

By the late 18th and beginning of 19th century, some scientists were busily investigating how animals get their colors and how do they change colour in response to the environment. They identified several types of chromatophores, i.e. cells that contain pigments. Biological pigments are called melanins (don’t confuse them with melatonin). One of these cells is the melanophore which contains black pigments, called this way in the very typical scientist unimaginative style because “melas” in Greek means black or dark and “phoros” means carrier.

A couple of these scientists, McCord & Allen (1917), thought that the pineal gland from the brain might contain some substance that might interact with the melanophores. How did they get this idea is unclear from their paper; seems like a logical outcome of their contemporaries’ discussions and experiments, though they do not explain it in detail. They hint of other experiments where various glands have been fed to amphibians and then noticed their color change. So McCord & Allen obtained cow brains, extracted the pineal glands and fed them to tadpoles. Within 30 to 60 minutes, depending on the concentration, the tadpoles fed with pineal extract changed color from dark to light (see picture).

mccord1917 - Copy
Excerpt from McCord & Allen (1917, doi: 10.1002/jez.1400230108) showing the change in tadpole skin appearance after application of bovine pineal gland extract.

Fast forward now to 1958 when an MD PhD called Aaron B. Lerner with an interest in dermatology thought that whatever was responsible for the skin color changes in the McCord & Allen (1917) paper might be useful in treating skin diseases. But first he had to extract the substance from the pineal glands and he and his colleagues had better tools for this task than the mere alcohol and acetone of his brethren of 40 years ago.

Lerner et al. (1958) made full use of the then-recently discovered paper chromatography and some standard biochemistry techniques for the time like Soxhlet extraction and fluorescence spectroscopy and discovered a substance that can lighten frog skin color and can inhibit the melanocyte stimulating hormone (MSH). “It is suggested that this substance be called melatonin” (p. 2587). Lerner and his colleagues also isolated the MSH and cryoglobulin.

Changing skin color is one of melatonin’s minor roles; its main function is to regulate circadian rhythms like sleep and awake cycles in animals (it has an oxidative stress protection in plants). Melatonin, in animals, is produced by the pineal gland only, more during the night, less during the day. Pineal gets information about the day/night cycles from the eyes. In some countries melatonin is sold as an over the counter soporific, i.e. sleeping pill.

Melatonin - Copy

REFERENCES:

1) McCord CP & Allen FP (Jan 1917). Evidences associating pineal gland function with alterations in pigmentation. Journal of Experimental Zoology, Part A, 23 (1):  207–224, DOI: 10.1002/jez.1400230108 ARTICLE 

2) Lerner AB, Case JD, Takahashi Y, Lee TH, & Mori W (May 1958). Isolation of Melatonin, the Pineal Gland Factor that Lightens Melanocytes. Journal of the American Chemical Society, 80 (10), p. 2587–2587, DOI: 10.1021/ja01543a060 ARTICLE (although JACS gives access only to the first page of a paper, the fact that this article is only half a page makes their endeavour useless in this case)

By Neuronicus, 18 March 2017

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