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“Opposition is true friendship.”
Melatonin is generally most associated with the Pineal gland where it is produced in most vertebrates. It is produced in many other tissues as well as being present in plants. It appears to be an ancient molecule occurring in unicellular organisms at a very early stage of Life.
Melatonin is found in large amounts in the mitochondria the locus of energy generation within the cell, it has been suggested that it is in the mitochondria where it’s synthesis occurs.
The most simple pineal complex found in vertebrates, that of the lamprey consists of foldings of the diencephalic roof and has a retina like structure containing photoreceptor cells and secondary neurons. In more complex vertebrates the folding is multiplied (Vigh et al. 1998). The mammalian pineal gland itself is generally considered to be light insensitive, modern birds and reptile pineal glands contain the phototransducing pigment melanopsin.
The Pineal organ is located in the geometric centre of the brain in most mammals including humans where it is roughly the size of a grain of rice. Historically it has often been considered significant and in Yoga it is sometimes said to be the physical manifestation of Sahasrara chakra (the Crown).
The Pineal gland while in the centre of the brain exists outside of the blood-brain barrier, located at the rear of the third ventricle and a portion of it is in direct contact with the cerebrospinal fluid (CSF) this explains the much higher levels of melatonin in CSF than in circulation. Tan et al. 2016 suggest that the pineal gland may play a role in the circulation of CSF as well as it’s generation.
The Pineal gland is highly vascularised multiple arteries deliver blood to this little organ. At least in rats the minimum rate of pineal blood flow per gram tissue exceeds that of most endocrine organs. The rate of pineal blood flow is 16 times higher than that of the average gram of tissue in rats.
Tan et al. 2016 suggest that this high rate of blood flow points to both a metabolically active gland and one with a secretory role. The Pineal anterior collecting vein has a constriction point before emptying, sphincters may be present here regulating blood flow within the gland, the increase in pressure might allow increased CSF and melatonin secretion. The tissue of the pineal gland may have a higher rate of filtration than the renal glomerulus (Tan et al. 2016).
Melatonin levels generally appear to decline during the day, because it’s synthesis occurs at night melatonin has been called the chemical expression of darkness. It may be involved in dreaming some people who have taken it as a supplement report vivid dreams.
Melatonin is an indolamine derived from tryptophan with serotonin as an intermediate. Short wavelength light in the blue end of the spectrum inhibits the activity of arylkylamine N-acetlytransferase the penultimate enzyme that converts serotonin to melatonin. Longer wavelength light in the red, orange, and yellow part of the spectrum does not appear to inhibit melatonin synthesis (Wright et al. 2004). The light is believed to act via neural pathways from the retina through the suprachiasmatic nucleus to the pineal.
In addition to melatonin the pineal gland secretes other substances including the beta-carboline pinoline and the tetrapeptide epithalamin. The Pineal organ may also be a source of the potent psychedelic DMT though this is still unconfirmed, the related 5-MeO-DMT does seem to be found in human pineal gland and DMT does occur in small quantities in human cerebrospinal fluid (Smythies et al. 1979).
Damage to the pineal gland can result in precocious puberty, premature development of the sex organs and skeleton.
Some bats appear to have unusually large pineal glands, relative to body mass the New Guinea naked backed bat Dobsonia praedatrix may have the largest pineal gland of any animal (Bhatnagar et al. 1990). The vampire Desmodus rotundus has a large pineal with complex structure and an ultrastructure unlike any other reported mammal.
Melatonin seems to have a wide range of beneficial actions many of these seem to be a result of its antioxidant activity. Melatonin protects against gamma radiation, reducing rates of edema, necrosis, and neuronal degeneration (Erol et al. 2004). In a study using blood from human volunteers melatonin decreased chromosome aberrations as a result of radiation exposure (Reiter et al. 1996). Melatonin protects from ultraviolet radiation, cells treated with melatonin showed increased survival rates and decreased formation of the lipid peroxide malondialdehyde (Ryoo et al. 2001). Melatonin inhibited lipid peroxide production and tissue damage as a result of mercury exposure (Sener et al. 2003). Melatonin inhibits lipopolysaccharide induced nitric oxide activation (Escames et al. 2003).
Do what thou wilt shall be the whole of the Law.
Melatonin seems to exert multiple pro mitochondrial effects, promoting mitochondrial fusion and inhibiting mitochondrial fission (Parameyong et al. 2013 and Pei et al. 2016). Melatonin promotes the activity of respiratory complexes I and IV, counteracting respiratory inhibition induced by potassium cyanide (Martin et al. 2002). In a mouse model of accelerated aging melatonin increased life span and improved mitochondrial function lowering lipid peroxidation (Rodriguez et al. 2008).
Melatonin increases brown adipose tissue (BAT) fat tissue characterised by increased mitochondrial density, it is involved in heat production generally increased levels occur in youth. BAT appears to be a characteristically mammalian tissue and has not been found to occur in the vast majority of other vertebrates. Melatonin also appears to increase the metabolic activity of BAT mitochondria and may play a role in weight regulation (Tan et al. 2011). Melatonin increased the expression of uncoupling protein UCP1 and PGC1A by up to 2 fold (Jimenez-Aranda et al. 2013). PGC1A is a human accelerated region involved in mitochondrial biogenesis and maintaining oxidative characteristics of muscle fibres promoting type 1 slow red postural fibres.
Given the centrality of energy generation in every aspect of biology melatonin should be expected to exert multiple protective effects on the organism there is evidence that this is so.
Melatonin protects against fibrosis in seemingly all tissues. Melatonin acts at all stages of fibrosis inhibiting injury of epithelial cells in the initial phase , reducing inflammatory cell infiltration and deposition of collagen (Hu et al. 2016). Melatonin also seems to be able to reverse fibrotic changes (Dominguez-Rodriguez et al. 2016).
Melatonin reduced cerebral edema in rats preserving the integrity of the blood-brain barrier (Gorgulu et al. 2001). Reduces pulmonary edema (Chen et al. 2015).
Melatonin appears to be therapeutic in cancer, reducing the number of prostate cancer cells, stopping cell cycle progression and inducing cellular differentiation (Sainz et al. 2005). In neuroblastoma cancer cells melatonin produced greater neuritis outgrowth and more differentiated cells (Cos et al. 1996). Concentrations of melatonin corresponding to physiological levels present in human blood during the evening hours significantly inhibited by up to 78% cell proliferation in a breast cancer cell culture model (Hill and Blask 1988). Cells showed improved morphological characteristics with reduced nuclear swelling and disruption of mitochondria. Melatonin reduced invasiveness of cancer cells, inhibiting the effects of estradiol on cell adhesion and cell migration (Cos et al. 1998).
Melatonin seems to be able to inhibit aromatase, which converts testosterone into estradiol (Chottanapund et al. 2014).
In mice melatonin reverses age related thymic involution (Tian et al. 2001). The thymus is a lymphoid organ found in the chest behind the sternum and in front of the heart, it is where T cells a type of white blood cell mature, it is at its largest in children and generally shrinks from puberty onwards. Removal of the pineal gland in newborn rats resulted in disorganisation of the thymus and malignant transformation. The thyroid also showed tissue changes with increased deposition extracellular matrix (Csaba and Barath 1975).
Melatonin also protects against the effects of snake venom, including cobras and vipers, Melatonin reduced haemorrhage, muscle necrosis, damage to liver, kidneys and lungs, levels of nitric oxide, lipid peroxides, and inflammation (Katkar et al. 2014, Moneim et al. 2015, Al-Sadoon et al. 2016).
Melatonin appears to have significant morphogenic effects removal of the pineal organ can produce scoliosis in chickens (Wang et al. 1998 and Turgut et al. 2005). In humans scoliosis appears to be associated with significantly lower melatonin levels (Machida et al. 1996 and Sadat-Ali et al. 2000).
Melatonin may be involved in tooth development as rat dental cells appear to express melatonin “receptors”(Kumasaka et al. 2010).
Melatonin stimulates synthesis of type 1 collagen in human bone cells in vitro (Nakade et al. 1999), bone strength is determined not only by bone mineral density but also by the protein matrix woven into the bone including collagen and other proteins.
The Starchild skull amongst its unusual features appears to consist of a thin but super strong bone reinforced by protein fibres, might an enlarged or more developed Pineal organ and increased melatonin have played a role in these traits?
Melatonin enhanced differentiation of mesenchymal stem cells into chondrocytes, increasing the size and GAG production of cartilage tissue (Gao et al. 2014).
Melatonin preserves the integrity of the blood-brain barrier and protects against hydrocephaly (Turgut et al. 2007). Low melatonin is associated with hydrocephaly (Yamada et al. 1991).
Melatonin decreases with age and the pineal organ accumulates calcium and fluoride (Luke 2001 and Kunz et al 1999).
Calcification of the pineal organ is associated with decreased melatonin production and Alzheimer’s disease, significantly more pineal tissue is calcified in Alzheimer’s than in other types of dementia (Mahlberg et al. 2008).
There is some evidence for a sort of cardio-pineal axis mediated by melatonin and the natriuretic peptides (ANP, BNP, and CNP) secreted by the heart, other substances and subtler interactions might also be involved.
Love is the law, love under will.
Post infarction (heart attack) long-term melatonin supplementation elevates expression of ANP (a heart hormone) from the left ventricle in rats (Sallinen 2008).
A small study using only 6 individuals found some evidence that ANP might increase melatonin, in two individuals serum melatonin levels doubled in response to ANP (Lissoni et al. 1990).
The Pineal gland also appears to contain CNP (Middendorff et al. 1996). In the pineal gland the natriuretic peptides elevate cyclic GMP levels (Olcese et al. 1994).
Impaired nocturnal secretion of melatonin occurs in coronary heart disease (Brugger et al. 1995).
The Pineal organ is highly vascularised richly supplied by blood vessels with one of the highest rates of blood flow of any tissue (below that of the carotid body and maybe the kidney and thyroid) with such an extensive blood supply it seems inevitable that a relationship between the heart and pineal gland must exist.
As the pineal organ exists outside of the blood-brain barrier it might be especially easy to increase blood flow to it using inversions such as headstand and shoulderstand, meditation seems likely to be helpful. Yoga and meditation have been found to increase melatonin levels (Harinath et al. 2004).
Do what Thou wilt shall be the whole of the Law.
Love is the Law, Love under Will.
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