Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina

Bernard, Marianne; Guerlotté, Jérôme; Grève, Pierre; Gréchez-Cassiau, Aline; Iuvone, Michael; Zatz, Martin; Chong, Nelson W.; Klein, David C.; Voisin, Pierre

doi:10.1051/rnd:19990305

Cited by 67 publications

(30 citation statements)

References 39 publications

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“…Melatonin is produced rhythmically by photoreceptive pinealocytes within the pineal gland and by the retinal photoreceptor layer during the night, when animals are placed in light:dark (LD) cycles; the rhythmicity persists when animals are maintained under constant environmental conditions such as continuous darkness (DD) Bernard et al, 1999). In chickens, this rhythm is due primarily to the daily and circadian regulation of transcription of genes encoding key enzymes in the melatonin biosynthetic pathway in vivo and in vitro .…”

Section: Introductionmentioning

confidence: 99%

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Adachi

Natesan

Whitfield-Rucker

et al. 2002

Glia

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Melatonin is an important hormone regulating circadian clocks in birds, but the specific cellular sites of action are not completely known. The present study was designed to determine whether astrocytes derived from chick brain contained functional melatonin receptors. Primary cell cultures of diencephalon astrocytes that express glial fibrillary acidic protein (GFAP), but not neuron-specific enolase (NSE) immunoreactivity, were employed to determine the cellular distribution and physiological role for the three known receptor subtypes. Saturation and Scatchard analysis of 2-[(125)I]iodomelatonin binding demonstrated melatonin receptor binding with a high affinity and a pharmacological profile similar to that obtained from brain. In situ hybridization for receptor subtypes revealed Mel(1A) and Mel(1C) receptor mRNA, but not Mel(1B). Administration of pharmacological levels of melatonin acutely inhibited forskolin-stimulated 2-deoxyglucose (2DG) uptake, while rhythmic administration of physiological levels of melatonin gradually imposed a rhythm in 2DG uptake and of the release of both lactate and pyruvate into the medium. These results indicate that (1) there are functional Mel(1A) and Mel(1C) melatonin receptors in astrocyte-rich cultures, and (2) rhythmic administration of melatonin plays an important role in the regulation of astrocytic metabolic activity. Together, the data suggest that the circadian secretion of melatonin probably plays a role in the global metabolic economy of the avian brain through rhythmic regulation of metabolism in astrocytes.

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Section: Introductionmentioning

confidence: 99%

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Adachi

Natesan

Whitfield-Rucker

et al. 2002

Glia

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“…One of them is the synthesis of the neurohormone melatonin [Guerlotté et al, 1996]. Melatonin synthesis is strictly coupled to the presence of photosensitive structures, therefore its production is restricted to the pineal gland and the retina [Korf, 1994;Korf et al, 1998;Bernard et al, 1999;Iuvone et al, 1999]. Whereas melatonin derived from the pineal gland circulates throughout the organism to influence many physiological functions, like locomotor activity or reproduction [Arendt, 1995], retina-borne melatonin acts more locally.…”

Section: Introductionmentioning

confidence: 99%

Light-Dark and Circadian Melatonin Rhythms Are Established de novo in Re-Aggregates of the Embryonic Chicken Retina

Willbold

Huhn²,

Korf³

et al. 2002

Dev Neurosci

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A central function of chicken photoreceptors is the rhythmic synthesis of the neurohormone melatonin; however, it is unclear how they can achieve – already before hatching (i.e. without light exposure) – a circadian pacemaker system. Here we studied melatonin synthesis and secretion in rosetted spheroids, which are de novo histotypic spheres, re-aggregated from dissociated retinal cells of chicken embryos. Spheroids were cultured during a 12-hour light/12-hour dark cycle. Shortly after the onset of photoreceptor differentiation in spheroids near day 5 in culture, melatonin secretion set in and, by day 8 in culture, showed distinct dark-light oscillations, with high values during the dark and lower ones during the light period. Concomitantly, expression of two key enzymes of melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was detected by northern blot analysis from day 6 onwards, increasing until day 8. Only HIOMT, but not AA-NAT levels were 2- to 3-fold higher at the end of the light compared with the dark phase. Even under permanent darkness, a slight melatonin oscillation was revealed after 6 days. In conclusion, photoreceptors in de novo regenerated retinal spheroids become light-responsive, establish appropriate pathways for melatonin synthesis and secrete more melatonin in the dark. The underlying circadian pacemaker seems to depend on photoreceptor differentiation, not on previous light-dark entrainment.

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“…Moreover, exposure to light during the first 6 h of the night inhibited the nocturnal increase in Aanat mRNA level. The same research group reported day/night changes in the expression of Tph1, Aanat and Asmt genes both in the pineal glands and in the chicken pineal cultures as well as day/night changes in Tph1 and Aanat expression in the chicken retina (Bernard et al, 1999). According to TABLE 7.…”

Section: Discussionmentioning

confidence: 94%

“…This discrepancy may be due to differences in the experimental procedure employed, which in the present study was focused on the age and season of hatch of the animals. In the earlier microarray analysis of the chicken pineal transcriptome, 7-d-old animals were used (Bailey et al, 2003), whereas the in vitro analyses of gene expression were performed with pineal glands taken from 1 or 2-d-old animals (Bernard et al, 1997(Bernard et al, , 1999Florez et al, 1996), and older animals were used for the in vivo analysis (Bernard et al, 1999). Moreover, in the aforementioned papers, the season of hatch was not taken into consideration.…”

Section: Discussionmentioning

confidence: 99%

Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland

Piesiewicz

Kędzierska

Turkowska

et al. 2014

Chronobiology International

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Previously, we have demonstrated the postembryonic development of chicken (Gallus gallus domesticus L.) pineal gland functions expressed as changes in melatonin (MEL) biosynthesis. Pineal concentrations of MEL and its precursor serotonin (5-HT) were shown to increase between the 2nd and 16th day of life. We also found that levels of the mRNAs encoding the enzymes participating in the final two steps of MEL biosynthesis from 5-HT: arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as their enzymatic activities, were raised during postembryonic development. Moreover, the manner of these changes was season-of-hatch dependent, even in animals kept under constant laboratory conditions (L:D 12:12). The most pronounced changes were seen in the concentrations of 5-HT and MEL, as well as in Aanat mRNA level and its enzymatic activity. The high daily variability in 5-HT content suggested that season- and age-dependent changes in the activity of the chicken pineal gland might rely on the availability of 5-HT, i.e. it may be limited by changes in pineal tryptophan (TRP) and/or 5-hydroxytryptophan (5-HTP) levels as well as by the activity of tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC): two enzymes participating in the conversion of TRP to 5-HT. The present study was undertaken with the following objectives: (1) to examine whether the pineal concentration of the 5-HT precursors TRP and 5-HTP exhibit age- and season-related changes; (2) to look for season-related differences in the transcription of the Tph1 and Ddc genes encoding enzymes TPH and AADC; (3) to identify the step(s) in postembryonic development in which these season-related variations in pineal gland function are most pronounced. Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held in L:D 16:8 conditions were kept from the day of hatch in L:D 12:12 conditions. At the age of 2 or 9 days, animals were sacrificed every 2 or 4 h over a 24-h period and their pineal glands were isolated under dim red light and processed for the measurement of (i) the pineal content of TRP, 5-HTP and 5-HT, and (ii) the level of Tph1 and Ddc mRNAs. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The pineal levels of TRP and 5-HT as well as the Tph1 and Ddc transcripts changed during postembryonic development in a season-related way. Whereas, the 5-HTP concentration did not vary between animals from both age groups, regardless of the season. Circadian rhythmicity of all the measured parameters was dependent on both the age and the season of hatch, and was greatest in older animals in the summer. These findings indicated that the efficiency of season-related MEL biosynthesis, reported previously, is limited by 5-HT availability and this limitation depends on the transcription of both the Tph1 and Ddc genes. Moreover, Ddc mRNA level in 9-d-old birds changed rhythmically, even though this gene is generally considered to be arrhythmic.

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Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina

Cited by 67 publications

References 39 publications

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Light-Dark and Circadian Melatonin Rhythms Are Established de novo in Re-Aggregates of the Embryonic Chicken Retina

Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland

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