Photoperiodic control of the seasonal variations in the daily pattern of melatonin synthesis in the European hamster, Cricetus cricetus.
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Animals↗
Biomedical subjects
P Pevet
Publications and source records attributed to P Pevet.
Direct vasoactive intestinal polypeptide-containing projection from the suprachiasmatic nucleus to spinal projecting hypothalamic paraventricular neurons.
In mammals, photoperiodic information is conveyed from the retina to the pineal through a polysynaptic pathway, which includes the suprachiasmatic nucleus (SCN), the paraventricular nucleus of the hypothalamus (PVN), the spinal preganglionic neurons and, finally, the superior cervical ganglion. Precise data on the site in the PVN or which SCN transmitters are involved in the transmission of information in this pathway is lacking. In the present experiment we investigated whether SCN efferents containing vasoactive intestinal polypeptide (VIP) innervate PVN neurons that project to the spinal cord. A combination of retrograde tracing and immunocytochemistry with the aid of a confocal laser scanning microscope allowed us to assess possible interaction of SCN efferents and spinal cord projecting neurons in the PVN. Approximately 30% of identified autonomic projecting neurons in the dorsal PVN and 40% in the ventral PVN received VIP innervation mainly on their dendrites. These results provide further evidence for the involvement of SCN-derived VIP in the transmission of circadian information to the pineal.
Animals↗
Effect of prolonged fasting and subsequent refeeding on free-running rhythms of temperature and locomotor activity in rats.
This study investigated the possible effect(s) of prolonged fasting and subsequent ad lib refeeding on the circadian organization of rats kept in constant darkness. Free-running rhythms of wheel-running activity and body temperature were studied in rats fasted during a 7-day interval followed with ad lib refeeding started either at subjective midday, i.e., CT6 (circadian time 6) or subjective midnight, i.e., CT18. Phase-shifts of temperature acrophases were similar to those of activity acrophases. During fasting, phase-shifts were phase-advanced (1 circadian h on the average) in most cases. During refeeding, they were mostly phase-delays (2 circadian h on the average) independently of the circadian time of refeeding, i.e., ad lib refeeding did not act as a Zeitgeber. In conclusion, prolonged fasting and subsequent refeeding induce opposite effects on the circadian organization.
Animals↗
The role of the intracellular and extracellular serotonin in the regulation of melatonin production in rat pinealocytes.
This study investigated whether the activation of pinealocyte beta-adrenergic receptors is involved in the regulation of serotonin (5-HT) synthesis and release, as it is for melatonin production. In addition, the role of the intra- and extra-cellular 5-HT in modulating the synthesis of melatonin induced by the beta-adrenergic agonist isoproterenol (ISO) was also studied. The incubation of dissociated pinealocytes with 0.1-10 microM ISO resulted in a concentration-dependent increase of melatonin synthesis. 5-HT release and intracellular 5-HT content were increased by 0.1 and 1 microM ISO but they were reduced after ISO 10 microM. Moreover, when incubated with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA), the secretion of 5-HT as well as the intracellular 5-HT levels were markedly reduced in both ISO-stimulated and unstimulated conditions. Melatonin release was also inhibited by PCPA, although it responded in the expected manner to increasing concentrations of ISO. These data indicate that the release of 5-HT from pinealocytes depends on the availability of cytoplasmic 5-HT, which in turn is highly dependent on the tryptophan hydroxylase activity. In cells stimulated with moderate ISO concentrations, 5-HT release may be an important regulatory process of pineal 5-HT. After a large stimulation of N-acetyltransferase (NAT) activity by ISO, the synthesis of melatonin prevails on 5-HT release, whose decrease is associated to a deficit of intracellular 5-HT. On the other hand, the present study shows that the incubation of pineal cells with high concentrations of 5-HT or with a selective 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine, reverses partially the inhibitory effect of PCPA on the ISO-stimulated melatonin synthesis. In contrast the 5-HT2 antagonist, ketanserin, results in an inhibiton of the release of melatonin following ISO stimulation. These results suggest that released 5-HT may have a role in the full expression of the beta-adrenergically induced NAT activity and, thus, may contribute to the optimal melatonin synthesis at night.
Adrenergic beta-Agonists↗
Sexual diversity of the lipid metabolism in the Harderian gland of the golden hamster.
Fatty acid and alkyl compositions of 1-alkyl-2,3-diacylglycerols (ADG) in the Harderian gland of the golden hamster were determined. Fatty acids of male ADG consisted of straight chain saturated acids ranging from C12 to C22. Both even- and odd-numbered acids were observed, indicating that acetyl- and propionyl-CoAs were equally used as primers in the fatty acid synthesis. In female ADG a large amount of iso- and anteiso-branched fatty acids were detected. Odd-numbered acids (C15, 17, 19, and 21) contained iso- together with anteiso-branchings, and even-numbered acids (C16 and 18) contained iso-branchings. These findings suggested that isobutyryl-, isovaleryl-, and 2-methylbutyryl-CoAs were used as primers in addition to acetyl- and propionyl-CoAs in fatty acid synthesis in the female gland. Such unusual primers are catabolic intermediates of valine, leucine, and isoleucine, respectively. Male ADG contained straight chain saturated alkyl residues ranging from C14 to 21. In the case of female ADG, though the main component was C18:O, most alkyl components had branchings at the iso- and anteiso-positions. NMR data suggested the presence of propionic acid at the C3 position of glycerol in the male ADG and of isovaleric and 2-methylbutyric acids at the same position in the female ADG. These results suggest that the sexual differences of the lipids in the Harderian gland of the golden hamster are determined at the step of fatty acid synthesis depending on the available precursors in the male and female glands. We speculate that sex hormones affect the metabolism of branched chain amino acids and bring about the dramatic diversities of the lipid compositions in the male and female glands.
Amino Acids↗
Circadian photic regulation of melatonin receptor density in rat suprachiasmatic nuclei: comparison with light induction of fos-related protein.
High-affinity melatonin receptors are present in rat suprachiasmatic nuclei (SCN), and their density exhibits a daily rhythm regulated by the light/dark cycle. In this study we demonstrate that the light regulation of these receptors depends on a circadian mechanism. Pinealectomized rats kept in constant darkness were subjected to 1-hr light pulses delivered across the circadian cycle. The density of melatonin receptors was significantly increased when photic exposure was performed during subjective night, and not different from control animals kept in darkness when the light pulse was applied during subjective day. The protein product (Fos) of the immediate early gene c-fos studied in the same paradigm showed globally the same circadian sensitivity phase. These results clearly show that, although the rhythmic appearance of melatonin receptor density in SCN follows and is directly regulated by the standard light/dark cycle, this light regulation is not passive. As is the case with Fos-like protein, it is only during a precise phase of the circadian cycle that light is able to regulate the density of melatonin receptors in SCN.
Animals↗
The suprachiasmastic nucleus: the biological clock of all seasons.
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Animals↗
Sexual dimorphism of lipids in Harderian glands of golden hamsters.
The Harderian gland of golden hamsters excretes alkyldiacylglycerol (ADG), the fatty acid and alkyl compositions of which differ between males and females. ADG in males contains mostly straight chain fatty acids, even- and odd-numbered, the major one being 15:0, while ADG in females contains iso- and anteiso-branched chain acids (34.0%). Iso-branching was found in both even- and odd-numbered acids, but anteiso-branching was found mostly in odd-numbered acids. The presence of propionic acid at the 3 position of the glycerol moiety in male ADG, and of isovaleric and 2-methylbutyric acids at the same position in female ADG was demonstrated by NMR spectrometry. Alkyl portions also exhibited sexual dimorphism in these lipids. ADG from males consisted of straight aliphatic chains, but branched chain components occupied almost half (45%) in ADG from females, and the branching resided at the iso- and anteiso-positions. The ADGs in glands from the two sexes were separated by Iatrobeads column chromatography into three and two subfractions, respectively. The fatty acid and alkyl compositions of these subfractions coincided with the above-mentioned results and with the behavior of the ADGs on thin-layer plates. These findings suggest that a sex hormone affects the metabolism of valine, leucine and isoleucine, and sexual dimorphism of ADGs occurs in the Harderian gland.
Animals↗
The photoperiodic response in Syrian hamster depends upon a melatonin-driven circadian rhythm of sensitivity to melatonin.
The pineal gland, via the daily pattern of melatonin (MEL) secretion, is directly involved in the conduction of photoperiodic information. The duration of MEL secretion is proportional to the duration of the dark period and, whatever the photoperiod is, MEL synthesis occurs 3 or 4 h after the dark onset in Syrian hamsters. In order to determine the relative importance of the duration or the coincidence hypothesis, a daily infusion protocol was used in sexually active pinealectomized hamsters. Long duration of MEL infusion (10 h) completely inhibit testes whereas short duration infusion (5 h) had no effect. When the animals were infused twice within 2 h 30 min separated by 3 h, they presented a complete gonadal atrophy, similar to the one observed with the 10 h infusion. Measurement of plasma MEL during the infusion and separation periods revealed that MEL reached physiological nighttime values during the infusion period and fell to daytime values 1 h after the end of an infusion period. Thus, the results could not be due to a time additive action of the two MEL pulses. An intermediate response was observed when the 2 signals were applied across the light/dark transition. Gonadal regression did not occur when the 2 periods of infusion were separated by 5 h 30 min. The efficiency of this type of infusion was not dependent on the ambiant photoperiod since similar results were obtained in long and short photoperiods. The infusion was also as effective during the day as well as during the night. These results suggest that there is a rhythm of sensitivity to MEL, based on the coincidence hypotheses, that are important for transmission of photoperiodic information. This rhythm of sensitivity to MEL seems to be entrained by MEL itself, since the efficiency of the two pulses of MEL is not dependent of time of application and/or of photoperiod.
Animals↗
The decrease of pineal melatonin production with age. Causes and consequences.
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Aging↗
Daily variations in melatonin receptor density of rat pars tuberalis and suprachiasmatic nuclei are distinctly regulated.
Suprachiasmatic nuclei (SCN) and pars tuberalis (PT) are two structures in the rat exhibiting high affinity receptors for melatonin. Melatonin receptor density in these two structures was previously shown to be inversely related to endogenous ligand concentration, thus elevated at daytime. We now demonstrate that, in the PT, these daily variations are directly induced by the circadian rhythm of plasma melatonin concentration. Variations persist in constant darkness and can only be blocked by pinealectomy. Thus, autoregulation loop of melatonin receptors determines the circadian rhythm in PT melatonin receptor density. However, this process of desensitization does not determine the daily variations in SCN melatonin receptor density. Indeed, in the SCN, the light/dark cycle is the regulatory factor: melatonin receptor density was shown to be specifically reduced during the night even in pinealectomized animals, while one h light was shown to reverse this nocturnal decrease in the SCN. Moreover, this darkness-induced down-regulation of SCN melatonin receptors has a masking effect on the earlier shown ligand-dependent desensitization process in this structure. This explain why, in constant darkness, SCN melatonin receptor density did not show any variation throughout the 24 h subjective day and night, although the circadian rhythm of melatonin persisted. These results thus clearly show that although daily rhythms in the density of melatonin receptors are identical in the PT and in the SCN, their regulation is totally different in each of these two structures.
Animals↗
No high affinity melatonin binding sites are detected in murine melanoma cells and in normal human melanocytes cultured in vitro.
Saturation studies of 2-(125I)-iodomelatonin binding to membranes from normal human melanocytes, mouse melanoma cells B16F10 and amelanotic S91 revealed no specific binding. Using 2-(125I)-iodomelatonin in the concentration range of 6 to 566 pM, no high affinity melatonin binding sites were detectable in any of the cell types. Even when the concentration of radioligand was increased up to 2000 pM, specific binding was either low or absent and not reproducible. These results suggest that in the culture conditions used in this study, no high affinity melatonin binding sites are detected in pigmented cells.
Animals↗
[Present and future of melatonin in human and animal reproduction functions].
In the pineal gland, the photoperiodic information is translated into a chemical message, the nocturnal secretion of melatonin. The duration of this secretion is proportional to the length of the night and this is the way by which the photoperiodic information is integrated at the level of the central nervous system. It is now possible with melatonin to mime the effects of photoperiod on the reproductive axis. The daily melatonin secretion is directly generated in the circadian biological clock. Consequently, the periodic secretion of melatonin might be used as a circadian zeitgeber, able to entrain some circadian functions: it is thus possible to act with melatonin on circadian rhythms. At very large doses, melatonin seems to be able to act directly on gonads.
Animals↗
Sexual differences and seasonal variations in vasoactive intestinal peptide immunoreactivity in the suprachiasmatic nucleus of jerboa (Jaculus orientalis).
The sexual differences and the seasonal variation in the vasoactive intestinal peptide (VIP) content of the suprachiasmatic nucleus (SCN) of a desert rodent, the jerboa (Jaculus orientalis) were studied using immunocytochemical techniques. During the period of sexual activity (spring-early summer), the VIP immunoreactivity in the SCN was higher in females than in males. In the period of sexual quiescence (autumn), both males and females exhibited an even more intense VIP immunoreaction in the SCN as compared to spring. However, during this period, the sex-related differences in the VIP content of the SCN observed in spring were no longer detectable. The direct possible influence of sex hormones on the VIP content in the SCN, and the physiological significance of the seasonal variation observed in the VIP immunoreactivity in the SCN in this species remains to be determined.
Animals↗
Seasonal variations in the daily rhythm of pineal gland and/or circulating melatonin and 5-methoxytryptophol concentrations in the European hamster, Cricetus cricetus.
Day-night variations in pineal and/or circulating melatonin and 5-methoxytryptophol (5-ML) concentrations were measured monthly throughout the year in female European hamsters, Cricetus cricetus, maintained under natural conditions. Pronounced seasonal variations in the day-night rhythm of both melatonin and 5-ML were observed. As previously reported for melatonin, the daily rhythm of both methoxyindoles disappeared in spring and early summer, while a clear day-night rhythm occurred in autumn, winter, and early spring. The amplitude of the day-night variations appeared to be maximum from October until January. An inverse relationship existed between the rhythms of melatonin and 5-ML.
Animals↗
Seasonal variations in pineal 5-methoxytryptophol (5-ML) concentrations and in the daily pattern of pineal 5-ML and melatonin in the desert rodent Jaculus orientalis: effect of prolonged illumination during the night.
Seasonal variations in daytime pineal 5-methoxytryptophol (5-ML) and in the daily pattern of both pineal 5-ML and melatonin concentrations were measured by radioimmunoassay in male and female jerboas, Jaculus orientalis. Pineal 5-ML content was found to be low in winter and spring and showed a short but marked increase in summer. A clear daily rhythm was present in pineal 5-ML in September, with high concentrations during daytime and low concentrations during nighttime. In May there was a considerable drop in the daytime values and a marked decrease in the amplitude of the rhythm, while in December the daily rhythm completely disappeared. On the contrary, a clear daily rhythm was observed for pineal melatonin in September, December, and May with high values during nighttime and low values during daytime; no differences in the amplitude of the rhythm could be observed. Illumination during early night prevented both the nocturnal decrease of 5-ML and the increase of melatonin in September; in May illumination had no clear effect on 5-ML, while it prevented the normal increase of melatonin. These results suggest a possible desynchronization between the regulation of 5-ML and melatonin synthesis and release, and stress the complexity of the mechanisms involved in the environmental synchronization of seasonal functions.
Animals↗
Day and nighttime concentrations of 5-methoxytryptophol and melatonin in the retina and pineal gland from different classes of vertebrates.
5-Methoxytryptophol (ML) and melatonin concentrations were determined by radioimmunoassay in the retinae and pineal glands of frogs (Rana esculenta), chickens (Gallus domesticus), quails (Coturnix coturnix), and European hamsters (Cricetus cricetus), killed in the afternoon (1500-1700 hr) and around midnight (2400-0200 hr). ML was only detectable in significant amounts in the frog retina. In the pineal gland ML levels showed the opposite profile to retinal ML, with measurable levels in the chicken, quail, and hamster and undetectable levels in the frog (less than 2.0 pg/gland). A significant day/night variation was observed in the bird pineal only, with higher levels occurring during the day. In contrast to ML, the interspecies variation in melatonin content was similar in the retina and pineal, with the highest concentrations occurring in the chicken greater than quail much greater than frog greater than hamster. Significantly higher night levels of melatonin were observed in the retina of the chicken and quail and in the pineal of the chicken, quail, and frog. The ratio of ML:melatonin concentrations in the retina and pineal also showed interspecies variations. In the birds the amount of ML was minimal in comparison with the amount of melatonin (1-4% retina; 0.3-12% pineal). The highest ML:melatonin occurred in the retina of the frog and in the pineal of the European hamster.
Animals↗
Tryptophan hydroxylase synthesis is induced by 3',5'-cyclic adenosine monophosphate during circadian rhythm in the rat pineal gland.
Tryptophan hydroxylase in the rat pineal gland undergoes diurnal rhythmic activity. Rat pineal glands exhibit increased tryptophan hydroxylase activity when incubated with a cyclic AMP analogue in vitro. Cyclic AMP-dependent protein kinase phosphorylates tryptophan hydroxylase, purified from rat brain, without any modification of its enzyme activity under our experimental conditions. Actinomycin D or cycloheximide decreases the stimulating effect of the cyclic AMP analogue on pineal tryptophan hydroxylase activity. Incubation of pineal glands in the presence of [35S]methionine showed a cyclic AMP-induced increase in tryptophan hydroxylase synthesis. These results explain the circadian rhythm of tryptophan hydroxylase activity in the rat pineal gland and suggest that the regulation of tryptophan hydroxylase expression by cyclic AMP occurs probably either at the translational level or via transient expression of a transcriptional regulatory element.
Animals↗