Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers

Rousseau, Andréas; Petrén, Sven; Plannthin, J.; Eklundh, Thomas; Nordin, Conny

doi:10.1007/s007020050208

Cited by 54 publications

(40 citation statements)

References 26 publications

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“…Considering that the total volume of rat cerebrospinal fluid is ϳ400 l (21), 2 l of the 28 nM icv-injected melatonin (which efficiently suppressed hepatic gluconeogenesis) might have yielded a final concentration of ϳ0.14 nM. This concentration is very similar to that observed in the cerebrospinal fluid of healthy volunteers (32). Interestingly, higher doses of icvinjected melatonin (140 nM) failed to increase glucose clearance after pyruvate load, although it still induced Akt phosphorylation.…”

Section: Discussionmentioning

confidence: 69%

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Faria

Kinote

Ignácio-Souza

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients. melatonin; gluconeogenesis; melatonin receptors; liver MELATONIN (5-methoxy-N-acetyltryptamine) is produced and secreted by the pineal gland in a circadian fashion, with peak levels during the dark phase of the light-dark cycle. The canonical function of melatonin is to transmit environmental information (i.e., the length of the dark period) to the living organism, thereby synchronizing the circadian clock in the hypothalamic suprachiasmatic nucleus (22). In vivo and in vitro experiments have demonstrated that melatonin also plays a role in energy homeostasis by regulating body mass and adiposity and leptin expression by adipocytes (1, 40). Glucose homeostasis is also altered by the absence of melatonin in such a way that pinealectomized rats display glucose intolerance and desynchronized circadian pattern of gluconeogenesis, hallmarked by increased nighttime glucose levels (17,18,23). Moreover, chronic melatonin administration has been shown to improve glucose homeostasis not only in pinealectomized rats but also in rats rendered insulin resistant by diet manipulation (16,33,34).Although it has been demonstrated that melatonin stimulates glucose uptake in adipocytes and skeletal muscle cells in vitro (10, 19), the precise mechanism by which this hormone reduces whole body glucose intolerance has not been determined precisely. In mammals, the effects of melatonin are mediated in part by specific high-affinity G protein-coupled receptors known as melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) (31). We have demonstrated previously that melatonin acts locally in the hypothalamus to activate the p...

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Section: Discussionmentioning

confidence: 69%

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Faria

Kinote

Ignácio-Souza

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…In the same way, also high concentrations of melatonin are also necessary to obtain oncostatic actions in neuroblastoma cells and other kinds of tumour cells (Sainz et al, 2005;García-Santos et al, 2006). Melatonin is a highly lipid-soluble indolamine which may easily cross the blood -brain barrier, and there is evidence that melatonin concentration in the cerebrospinal fluid is higher than in blood (Rousseau et al, 1999;Longatti et al, 2007). These high concentrations of melatonin in the cerebrospinal fluid may contribute to explain why high levels of melatonin are necessary to inhibit glioblastoma cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

et al. 2007

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Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT) -PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas.

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“…Once synthesized, the majority of melatonin diffuses directly towards the cerebrospinal fluid of the brain's third ventricle, while another fraction is released into the blood stream where it is distributed to all tissues and body fluids (Cheung et al 2006). It is found in serum, saliva (Cutando et al 2011, Novakova et al 2011, cerebrospinal fluids (Rousseau et al 1999), and aqueous humor of the eye (Chiquet et al 2006), ovarian follicular fluid, hepatogastrointestinal tissues (Messner et al 2001). Melatonin in the milk of lactating mothers exhibits a marked daily rhythm, with high levels during the night and undetectable levels during the day (Illnerova et al 1993, Sanchez-Barcelo et al 2011.…”

Section: Synthesis Distribution and Metabolismmentioning

confidence: 99%

Melatonin for Protection Against Ionizing Radiation

El-Missiry¹,

Othman²,

Al-Abdan³

2012

Current Topics in Ionizing Radiation Research

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Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers

Cited by 54 publications

References 26 publications

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Melatonin for Protection Against Ionizing Radiation

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