Genetic variability in plasma melatonin in sheep is due to pineal weight, not to variations in enzyme activities

Coon, Steven L.; Zarazaga, L.A.; Malpaux, Benoît; Ravault, J.P.; Bodin, Loýs; Voisin, Pierre; Weller, Joan L.; Klein, David C.; Chemineau, Philippe

doi:10.1152/ajpendo.1999.277.5.e792

Cited by 30 publications

(32 citation statements)

References 11 publications

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“…By referring to the multiple and step-to-step regression analyses, we can assume that the variation in the number of pinealocytes may explain about 80%, and the volume of pinealocytes about 20%, of the total variation in pineal weight. Thus, the difference between the two genetic groups of extreme lambs regarding their pineal weight at slaughter, already found in a previous experiment (Coon et al 1999), originated from a higher multiplication rate of pinealocytes rather than an enlargement of the same number of cells. This difference in number of pinealocytes was observed at slaughter, at 14 weeks old.…”

Section: Discussionmentioning

confidence: 60%

“…While the physiological significance of this genetic variability in melatonin secretion is unknown, investigations conducted regarding their physiological origin have demonstrated that such a variability comes from differences in the synthesis of melatonin from the pineal gland (Zarazaga et al 1998b). More specifically, this ability of the pineal gland is not related to enzymatic activity per mg of tissue, but to the size of the pineal gland, which can vary from 30 mg to more than 200 mg (Coon et al 1999). However, despite a well-established characterization of 'high secretors' and 'low secretors' of melatonin in adult sheep, we do not know whether this is due to differences in the number, or in the size, of pinealocytes in the pineal gland.…”

Section: Introductionmentioning

confidence: 99%

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Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep

Brunet

Malpaux²,

Daveau³

et al. 2002

Journal of Endocrinology

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Genetic variability in plasma melatonin concentrations in ewes results from variations in pineal weight. This study investigated whether it is due to a difference in the number of pinealocytes, or in their size. Two groups of lambs were assigned before birth to being extremes (18 High and 21 Low) by calculating their genetic value on the basis of the melatonin concentrations of their parents. Lambs were bled from 1 week of age until 14 weeks of age. Pineal gland, brain and pituitary weights, length and width of the brain, and length of the hypothalamus were recorded. A significant effect (ANOVA) of genetic group (P<0·05) and age (P<0·05) was detected on mean nocturnal plasma melatonin concentrations, as soon as the first week after birth (mean ...; High: 51·7 10·7 vs Low: 31·9 3·2 pg/ml). There was no difference between the two genetic groups in any of the brain parameters measured, but the pineal glands of the High group were heavier and contained significantly more pinealocytes (High: 27·8 2·4 vs Low: 21·0 2·4 10 6 ; P<0·05) than those in the Low group. The mean size of pinealocytes did not differ between the two genetic groups. Thus, the genetic variability in nocturnal plasma melatonin concentrations in sheep is expressed by 1 week of age and higher levels of secretion are the consequence of larger pineal glands containing a greater number of pinealocytes.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep

Brunet

Malpaux²,

Daveau³

et al. 2002

Journal of Endocrinology

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“…Anti-rat A ANAT 22-37 pT31 (As 3352), antioAANAT (As 3343), and anti-oAANAT (As 2819, also referred to as anti-AANAT 1-205 ) have been described (4,17,18). Antisera were immunopurified (19) by using synthetic phosphopeptide (As 3352, As 5901), unphosphorylated peptide (As 3343), or unphosphorylated protein (As 2819).…”

Section: Phosphorylation Of Expressed Andmentioning

confidence: 99%

“…5, which is published as supporting information on the PNAS web site) and does not detect unphosphorylated AANAT, oAANAT T31A S205G, or AANAAT pT31 S205A. Immunopurified anti-rat AANAT 22- (18). Additional details appear in the figure legends.…”

Section: Phosphorylation Of Expressed Andmentioning

confidence: 99%

Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N -acetyltransferase mediated by phosphoserine-205

Ganguly

Weller

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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199

189

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The nocturnal increase in circulating melatonin in vertebrates is regulated by the activity of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the melatonin pathway (serotonin 3 N-acetylserotonin 3 melatonin). Large changes in activity are linked to cyclic AMP-dependent protein kinase-mediated phosphorylation of AANAT T31. Phosphorylation of T31 promotes binding of AANAT to the dimeric 14-3-3 protein, which activates AANAT by increasing arylalkylamine affinity. In the current study, a putative second AANAT cyclic AMP-dependent protein kinase phosphorylation site, S205, was found to be Ϸ55% phosphorylated at night, when T31 is Ϸ40% phosphorylated. These findings indicate that ovine AANAT is dual-phosphorylated. Moreover, light exposure at night decreases T31 and S205 phosphorylation, consistent with a regulatory role of both sites. AANAT peptides containing either T31 or S205 associate with 14-3-3 in a phosphorylation-dependent manner; binding through phosphorylated (p)T31 is stronger than that through pS205, consistent with the location of only pT31 in a mode I binding motif, one of two recognized high-affinity 14-3-3-binding motifs AANAT protein binds to 14-3-3 through pT31 or pS205. Two-site binding lowers the K m for arylalkylamine substrate to Ϸ30 M. In contrast, single-site pS205 binding increases the K m to Ϸ1,200 M. Accordingly, the switch from dual to single pS205 binding of AANAT to 14-3-3 changes the K m for substrates by Ϸ40-fold. pS205 seems to be part of a previously unrecognized 14-3-3-binding motif-pS͞pT (X 1-2)-COOH, referred to here as mode III.pineal ͉ circadian ͉ cAMP ͉ kinase T he daily rhythm in circulating melatonin is a highly conserved feature of vertebrate physiology; in all cases, high levels occur at night. Day͞night differences in circulating melatonin levels provide a hormonal analog signal of environmental lighting, which is used in a variety of ways to optimize circadian and circannual rhythms in physiology (1). The melatonin rhythm is controlled by large changes in the rate of melatonin production in the pineal gland; these changes reflect changes in the penultimate enzyme in melatonin synthesis, arylalkylamine Nacetyltransferase (AANAT) (2, 3). Changes in the activity of this enzyme are strongly influenced by cAMP-dependent binding to the bowl-shaped, dimeric 14-3-3 protein (4, 5). Binding is thought to protect the enzyme against proteasomal proteolysis (6, 7); moreover, binding to 14-3-3 increases the affinity of AANAT by Ϸ10-fold for arylalkylamine substrates, e.g., serotonin and tryptamine (4, 5).Pinealocyte cAMP is controlled in mammals through a photoneural system, which includes the eyes and the suprachiasmatic nucleus, the site of the master circadian clock (1). In lower vertebrates, cAMP is regulated by light acting directly on pinealocytes (8). It is likely that cAMP-dependent binding to 14-3-3 occurs in all vertebrates, based on the ubiquitous presence of 14-3-3 proteins and the presence of two putative cyclic AMP-dependent protein kinase (PKA) sit...

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“…Mesurées dans le sang de la veine jugulaire, elles varient, dans l'espèce ovine, de moins de 50 pg/ml à 1000 pg/ml (Zarazaga et al 1998). Cette variabilité inter-individuelle, répétable et héritable, n'est pas due à des variations de l'activité des enzymes de synthèse de la MLT mais à la taille de la glande pinéale et au nombre de pinéalo-cytes qu'elle contient (Coon et al 1999). Les concentrations de MLT sont trois à cinq fois inférieures dans les artères caro-tides à celles constatées dans les veines jugulaires.…”

Section: La Mélatonine Est Présente En Fortes Concentrations Dans Le Lcrunclassified

Rôle du liquide céphalo-rachidien dans le transport de la mélatonine pinéalienne vers ses cibles centrales

Malpaux¹,

Legros²

2008

bavf

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La mélatonine, par sa durée nocturne de sécrétion, traduit les effets de la photopériode sur la reproduction. Dans cette revue, nous décrivons des résultats récents qui étayent l'hypothèse selon laquelle la mélatonine est transportée de la glande pinéale vers ses cibles cérébrales par le liquide céphalo-rachidien (LCR), plutôt que par le sang. Premièrement, la mélatonine est libérée dans le LCR en un site spécifique dans le recessus pinéalien où des pinéalocytes sont en contact direct avec le LCR. En conséquence, la mélatonine est présente à des concentrations environ 100 fois plus élevées dans le LCR que dans le sang. Deuxièmement, la mélatonine du LCR est capable de diffuser dans les tissus cérébraux rapidement et efficacement et peut donc atteindre des structures périventriculaires dans lesquelles des sites de liaison à la 2-iodomélatonine sont présents. L'ensemble de ces données conforte l'idée que la mélatonine du LCR est un signal physiologique pour le cerveau. Through the duration of its nocturnal secretion, melatonin is the primary transducer of photoperiodic information to the reproductive axis in seasonal breeders. In this review, we describe recent results supporting the hypothesis that melatonin, released by the pineal gland, reaches its central targets carried by cerebrospinal fluid (CSF), rather than blood. Firstly, melatonin is released in the CSF

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Genetic variability in plasma melatonin in sheep is due to pineal weight, not to variations in enzyme activities

Cited by 30 publications

References 11 publications

Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep

Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep

Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N -acetyltransferase mediated by phosphoserine-205

Rôle du liquide céphalo-rachidien dans le transport de la mélatonine pinéalienne vers ses cibles centrales

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