Melatonin Enters the Cerebrospinal Fluid through the Pineal Recess

Tricoire, H.

doi:10.1210/en.143.1.84

Cited by 110 publications

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“…The endogenous MEL, secreted from the pineal gland, is detected not only in the blood but also in the CSF in several species, such as non-human primates [22], sheep [25], goats [11] and cattle [9]. The existence of MEL in the CSF is very important, because MEL from the pineal gland is supposed to enter the CSF through the pineal recess [28], and would reach the peri-3V area, especially the hypothalamus, the presumable target site of MEL controlling the reproductive axis in sheep [16,18]. At this point of view, the injection of MEL into the 3V is an appropriate approach in order to evaluate the contribution of the hypothalamus to the effects of MEL on pituitary hormone secretion.…”

Section: Discussionmentioning

confidence: 99%

Effect of Melatonin Injected into the Third Ventricle on Growth Hormone Secretion in Holstein Steers

Kasuya

Kushibiki

Sutoh

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. The effects of melatonin (MEL) injection into the third ventricle (3V) on growth hormone (GH) secretion were investigated in conscious Holstein steers. A stainless steel cannula was stereotaxically implanted in the 3V based on the ventriculogram. In Exp. 1, three doses of MEL (100, 300 or 600 µg) were injected into the 3V through the cannula and the GH concentration after the injection was determined. In Exp. 2, intracerebroventricular (icv) and intravenous (iv) injections of MEL (100 µg) and GH-releasing hormone (GHRH; 0.25 µg/kg body weight), respectively, were performed simultaneously to examine the effect of MEL on GHRH-induced GH release. The icv injection of MEL significantly stimulated GH release at 100 µg. The increase in GH concentrations by 100 µg of MEL was persistent. Intravenous injection of GHRH dramatically increased GH release. The injection of MEL did not alter GHRH-induced GH release. These results suggest that MEL stimulates GH secretion possibly through the hypothalamus in cattle. KEY WORDS: cattle, melatonin, somatotropic axis, stereotaxic, third ventricle.J. Vet. Med. Sci. 68(10): 1075-1080, 2006 Growth hormone (GH) is a very important factor for livestock production [6]. GH-releasing hormone (GHRH) and somatostatin (SS) from the hypothalamus are primary factors controlling GH secretion in mammals. In addition to GHRH and SS, many neuromodulators have been considered to be involved in GH release regulation in many species. Although the central regulatory mechanism of GH secretion has been studied in sheep using hypophyseal portal blood sampling technique [4], such information is not well obtained in cattle.The evidences have shown the possibility that melatonin (MEL) from the pineal gland is one of those factors controlling GH secretion; however, the exact effect of MEL on GH secretion is controversial. For example, in humans it was reported that MEL induced an increase in GH levels [27,29]; however, other groups obtained no effects of MEL on GH secretion [13,31]. The intramuscular injection of MEL decreased GH secretion in prepubertal boys and the same dose of MEL increased GH level in some pubertal subjects [17]. In vitro experiments showed that MEL reduced GH secretion from rat pituitary cells [8]. These variations of the effects of MEL on GH secretion could be caused by the differences in the experimental and physiological conditions, and there might be inter-species differences regarding the role of MEL in the regulation of GH secretion.The purpose of the present study was to determine the role of MEL in the regulatory system of GH secretion in cattle. Since MEL has been reported to stimulate GH release via the hypothalamus [23,29], the technique for the direct injection of MEL into the third ventricle (3V) at three doses (100, 300 and 600 µg) was used. We also assessed whether MEL affects GHRH-induced GH release to reveal the involvement of the hypothalamus in GH secretion modulated by MEL. MATERIALS AND METHODS Animals:Eleven Holstein steers (7 to 8 mo old at the time of su...

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Section: Discussionmentioning

confidence: 99%

Effect of Melatonin Injected into the Third Ventricle on Growth Hormone Secretion in Holstein Steers

Kasuya

Kushibiki

Sutoh

et al. 2006

The Journal of Veterinary Medical Science

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“…The pineal release of melatonin is not restricted solely to the systemic circulation (Tan et al, 2003). There is compelling evidence to suggest that melatonin is also released via the pineal recess directly into the third ventricle, resulting in cerebrospinal fluid (CSF) melatonin levels greater than those detected in the systemic circulation (Tricoire et al, 2002). A gradient of CSF concentrations between the third ventricle and downstream CSF has been proposed, supporting the hypothesis that melatonin is rapidly absorbed into the central nervous system (Tan et al, 2003).…”

Section: Introductionmentioning

confidence: 96%

Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray

Seifman

Adamides

Nguyen

et al. 2008

J Cereb Blood Flow Metab

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Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F 2a (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28±0.92 versus 1.47±0.35 pg/mL, P < 0.0005). Isoprostane levels also increased in both CSF (127.62 ± 16.85 versus 18.28 ± 4.88 pg/mL, P < 0.0005) and serum (562.46±50.78 versus 126.15±40.08 pg/mL (P < 0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r = 0.563, P = 0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r = 0.369, P = 0.049) and glutamate (r = 0.373, P = 0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.

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“…This should be particularly important after administration of exogenous melatonin. To what extent the circulating hormone contributes, under physiological conditions, to its brain concentrations is not fully understood, specially as the pineal itself releases the indoleamine at much higher concentrations directly via the pineal recess to the third ventricle [146][147][148]. The appearance of melatonin in the third ventricle has been very recently demonstrated in humans, but the amounts reported are relatively moderate (about 8.75 pg/mL) [74].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Metabolism in the Central Nervous System

Hardeland¹

2010

114

110

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Abstract:The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P 450 subforms have been demonstrated in the brain. They either demethylate melatonin to Nacetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N 1 -acetyl-N 2 -formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N 1 -acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines.

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Melatonin Enters the Cerebrospinal Fluid through the Pineal Recess

Cited by 110 publications

References 0 publications

Effect of Melatonin Injected into the Third Ventricle on Growth Hormone Secretion in Holstein Steers

Effect of Melatonin Injected into the Third Ventricle on Growth Hormone Secretion in Holstein Steers

Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray

Melatonin Metabolism in the Central Nervous System

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