Present address: Department of Forensic Molecular Biology, Erasmus University Medical Centre Rotterdam, 3000 CA Rotterdam, the Netherlands.
A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases
Version of Record online: 26 APR 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 51, Issue 1, pages 17–43, August 2011
How to Cite
Stehle, J. H., Saade, A., Rawashdeh, O., Ackermann, K., Jilg, A., Sebestény, T. and Maronde, E. (2011), A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. Journal of Pineal Research, 51: 17–43. doi: 10.1111/j.1600-079X.2011.00856.x
- Issue online: 13 JUL 2011
- Version of Record online: 26 APR 2011
- Accepted manuscript online: 4 APR 2011 04:34AM EST
- Received October 20, 2010; Accepted December 16, 2010.
- acetylserotonin O-methyltransferase;
- arylalkylamine N-acetyltransferase;
- autoptic brain tissue;
- clock genes;
- neuroendocrine transducer
Abstract: The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone’s biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer’s disease, Smith–Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge.