Melatonin Content of the Pineal Gland in Different Mouse Strains

Goto, Maki; Oshima, Itsuki; Tomita, Takeshi; Ebihara, Shizufumi

doi:10.1111/j.1600-079x.1989.tb00667.x

Cited by 259 publications

(195 citation statements)

References 13 publications

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“…The C57BL/6 mouse strain has undetectable production of melatonin in the pineal gland, and very low-to-undetectable concentrations in plasma [42]. This is in agreement with the genetic defect in AANAT that led Roseboom et al [26] to postulate this mouse species as a natural melatonin ÔknockdownÕ.…”

Section: Discussionsupporting

confidence: 67%

Characterization of the serotoninergic system in the C57BL/6 mouse skin

Slominski

Pisarchik

Semak

et al. 2003

European Journal of Biochemistry

127

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We showed expression of the tryptophan hydroxylase gene and of tryptophan hydroxylase protein immunoreactivity in mouse skin and skin cells. Extracts from skin and melanocyte samples acetylated serotonin to N-acetylserotonin and tryptamine to N-acetyltryptamine. A different enzyme from arylalkylamine N-acetyltransferase mediated this reaction, as this gene was defective in the C57BL6 mouse, coding predominantly for a protein without enzymatic activity. Serotonin (but not tryptamine) acetylation varied according to hair cycle phase and anatomic location. Serotonin was also metabolized to 5-hydroxytryptophol and 5-hydroxyindole acetic acid, probably through stepwise transformation catalyzed by monoamine oxidase, aldehyde dehydrogenase and aldehyde reductase. Activity of the melatonin-forming enzyme hydroxyindole-O-methyltransferase was notably below detectable levels in all samples of mouse corporal skin, although it was detectable at low levels in the ears and in Cloudman melanoma (derived from the DBA/2 J mouse strain). In conclusion, mouse skin has the molecular and biochemical apparatus necessary to produce and metabolize serotonin and N-acetylserotonin, and its activity is determined by topography, physiological status of the skin, cell type and mouse strain.Keywords: mouse skin; serotonin acetylation; arylalkylamine N-acetyltransferase; tryptophan hydroxylase; hair cycle.The skin is the largest body organ and functions as a metabolically active biological barrier regulating internal homeostasis and separating the internal milieu from noxious environmental factors [1]. These functions are mediated by the skin immune, pigmentary, neuroendocrine, adnexal and vascular systems [1][2][3][4][5][6][7]. Most recently we have uncovered local serotoninergic and melatoninergic systems as novel elements of the cutaneous neuroendocrine components of human and hamster skin [8][9][10][11][12]. Serotonin is the product of a multistep metabolic pathway that starts with the hydroxylation of the aromatic aminoacid L-tryptophan by tryptophan hydroxylase (TPH) [13,14]. Serotonin can be acetylated by arylalkylamine N-acetyltransferase (AANAT) to N-acetylserotonin (NAS), which is further transformed to melatonin by hydroxyindole-O-methyltransferase (HIOMT) [13,15].Serotonin can act as a neurohormone, regulator of vascular tone, immunomodulator and growth factor, while melatonin can act as a hormone, neurotransmitter, cytokine or biological modifier [2,[15][16][17]. Some of these functions may be pertinent to skin physiology, which exhibits basic differences among the mammalian species. In rodents (mostly nocturnal animals) the skin is shielded from the damaging effect of solar radiation by fur [18], and the morphology of the entire mouse skin changes in close coordination with the cyclic activity of the hair follicle [19]. Mouse hair follicle cycling is characterized by a precisely regulated, time frame-restricted and differential pattern in the expression and activity of melanogenesis related proteins, PH, pterins and thioredoxin ...

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Section: Discussionsupporting

confidence: 67%

Characterization of the serotoninergic system in the C57BL/6 mouse skin

Slominski

Pisarchik

Semak

et al. 2003

European Journal of Biochemistry

127

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“…In this gland, melatonin is synthesized from serotonin via arylalkylamine N-acetyltransferase (AANAT), which produces rate-limiting intermediate N-acetylserotonin (NAS). In rodents, AANAT mRNA content (Roseboom et al, 1996;Uz et al, 2002b) and NAS and melatonin levels (Goto et al, 1989;von Gall et al, 2000) are marked by a circadian rhythm with high levels at night and low or even undetectable levels during the day. Recent findings indicate that the pineal gland also contributes to circadian cocaine sensitization; mice mutant for AANAT, whose pineal glands are incapable of synthesizing NAS and melatonin, do not show diurnal cocaine sensitization (Uz et al, 2002a).…”

Section: Introductionmentioning

confidence: 99%

The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Akhisaroğlu

Ahmed

et al. 2003

Neuropsychopharmacol

108

106

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Sensitization to psychostimulants can be influenced by circadian rhythms. The pineal gland, the main source of circadian melatonin synthesis, may influence behavioral sensitization to cocaine; mice with normal melatonin rhythms do not get sensitized at night. Clock genes such as Period1 (Per1) show rhythmic region-and strain-dependent expression in the mouse brain, and mice mutant for the Per1 gene lack cocaine sensitization. Here, for the first time we show circadian changes of PER1 protein levels in the mouse striatum, a brain region crucial for the development of locomotor sensitization to cocaine. In male C3H/HeJ mice, we found peak striatal PER1 protein levels during the day; this was preceded by a Per1 mRNA peak 16 h earlier. Pinealectomized mice did not show this circadian pattern. We analyzed circadian cocaine sensitization at times when striatal PER1 protein levels in control mice (naive and sham-pinealectomized) were high and low, respectively. Only mice with circadian changes in striatal Per1 expression showed the night-time absence of cocaine sensitization, whereas pinealectomized mice were without circadian changes in striatal Per1 and were sensitized to cocaine regardless of diurnal rhythm. Our results indicate that both the striatal circadian Per1 expression and diurnal locomotor cocaine sensitization are strongly influenced by pineal products. Since we found evidence for the expression of melatonin receptor mRNA in the striatum, we suggest that further studies on pineal-driven mechanisms will help us better understand the mechanisms of drug abuse and identify novel targets for the prevention and/or treatment of addictions.

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“…Because the pineal gland is a major target site for the SCN pacemaker, the experiment in a melatonin-deficient strain has restricted the usefulness of Cry genes for understanding the control of circadian rhythmicity. Mice of the C3H strain have the ability to synthesize melatonin and show circadian rhythms of melatonin concentration in both LD and DD (Goto et al 1989;VivienRoels et al 1998;Masana et al 2000). Therefore, in the current study, we evaluated the circadian variation and light responsiveness of pineal melatonin concentration in Cry1 ) ⁄ ) ⁄ Cry2 ) ⁄ ) mice on a C3H background.…”

Section: Introductionmentioning

confidence: 99%

Loss of circadian rhythm and light‐induced suppression of pineal melatonin levels in Cry1 and Cry2 double‐deficient mice

Yamanaka¹,

Suzuki²,

Todo³

et al. 2010

Genes to Cells

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Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm expression and acute lightinduced suppression of pineal melatonin was assessed using Cry1 and Cry2 double-deficient mice (Cry1 ) ⁄ ) /Cry2 ) ⁄ ) ) developed from the C3H strain that synthesizes melatonin. We examined the circadian variation of pineal melatonin under a 12:12-h light-dark (LD) cycle and constant darkness (DD). Light suppression of pineal melatonin concentration was analyzed by subjecting a 30-min light pulse at the peak phase of melatonin concentration. Wild-type mice showed significant rhythmicity in pineal melatonin concentration with the highest level at Zeitgeber time 22 (ZT22, where time of light on was defined as ZT0) under LD or ZT18 on the first day of DD. In contrast, Cry1 ) ⁄ ) /Cry2 ) ⁄ ) mice did not show significant circadian rhythmicity, with only a small peak observed at ZT22 in LD. Nevertheless, a significant daily variation could be observed under DD, with a small increase at ZT6 and ZT18 h. Melatonin concentration was significantly suppressed by acute light pulse at ZT22 in wild-type mice but not in Cry1 ) ⁄ ) /Cry2 ) ⁄ ) mice. The present results suggest that Cry genes are required for regulating pineal melatonin synthesis via circadian and photic signals from the suprachiasmatic nucleus of the hypothalamus (SCN).

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Melatonin Content of the Pineal Gland in Different Mouse Strains

Cited by 259 publications

References 13 publications

Characterization of the serotoninergic system in the C57BL/6 mouse skin

Characterization of the serotoninergic system in the C57BL/6 mouse skin

The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Loss of circadian rhythm and light‐induced suppression of pineal melatonin levels in Cry1 and Cry2 double‐deficient mice

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