Arrest of the circadian pacemaker driving the pineal melatonin rhythm in hibernating golden hamsters, Mesocricetus auratus

Pineal melatonin rhythm in golden hamsters was abolished during hibernation. After arousal in darkness, pineal melatonin increased rapidly regardless of whether the arousal was induced during the day or at night. Rapid increase of pineal melatonin after arousal was markedly diminished in animals exposed to light. In hamsters aroused at midnight, the melatonin rhythm in constant darkness ran with the reversed phase relative to hamsters aroused at noon. Since after arousal the melatonin rhythm obviously starts anew from the same phase, we conclude that the circadian pacemaker driving the rhythm might be arrested during hibernation at the day-time phase.     

Pineal melatonin rhythms in female Turkish hamsters: effects of photoperiod and hibernation

Daily rhythms of pineal and serum melatonin content were characterized for adult female Turkish hamsters (Mesocricetus brandti) exposed to long days (16L:8D, 22 degrees C) or after transfer to short days (10L:14D, 22 degrees C). The nocturnal peak of pineal melatonin content was found to be approximately 3 b greater in duration on short than on long days. Changes in levels of serum melatonin closely paralleled those of pineal melatonin. Thus, an effect of photoperiod on synthesis and secretion of pineal melatonin was demonstrated. In a separate experiment, female hamsters were induced to hibernate by exposure to a short-day, cold environment (10L:14D, 6 degrees C). During the 4 to 5-mo hibernation season, Turkish hamsters are known to display 4 to 8-day hours of torpor (body temperature = 7-9 degrees C) alternating with 1 to 3-day intervals of euthermia (body temperature = 35-37 degrees C). Little evidence of nocturnal synthesis or secretion of pineal melatonin was detected in females sampled during torpor. However, animals sampled during the first day after arousal from a torpor bout displayed melatonin rhythms no different in phase or amplitude from those seen in females held at 22 degrees C. Thus, despite the absence of pineal melatonin output during torpor, the pineal gland of hibernating Turkish hamsters produces an appropriately phased, rhythmic melatonin signal during intervals of euthermia.     

Decreases in pineal melatonin content during the hibernation bout in the golden-mantled group squirrel, Spermophilus lateralis

The role of the pineal gland in modulating the rhythmic bouts of hibernation in the golden-mantled ground squirrel (S. lateralis) was explored by comparing pineal melatonin content in hibernating animals with that of euthermic animals at the same time of year. Significant decreases in pineal melatonin content were found in hibernating versus euthermic animals. In addition, significantly lower values for pineal melatonin were observed in hibernating animals that were sacrificed in the late bout period, just prior to expected spontaneous arousal, as compared to hibernating animals that were sacrificed on the first day of their respective bouts. A strong correlation was evident between pineal melatonin content and the duration of the individual hibernation bout. These data suggest that pineal melatonin may be important in determining the duration of individual bouts of hibernation in this species.     

Daily rhythm in serum melatonin and leptin levels in the Syrian hamster (Mesocricetus auratus)

Melatonin is produced and secreted by the pineal gland in a rhythmic manner; circulating levels are high at night and low in the day. Leptin is a hormone secreted by adipocytes as a product of the obese gene and plays an important role in regulating body energy homeostasis and reproductive function in rodents and humans. The present study was conducted to examine daily fluctuations in serum levels of melatonin and leptin in Syrian hamster. We measured serum leptin and melatonin levels by ELISA in (a) intact and pinealectomized (pinx) male hamsters kept under long daylight conditions [14 h of light (14L)]; (b) intact and pinx hamsters under short daylight (10L); and (c) intact hamsters in constant light (24L). Blood samples were obtained every 2 h throughout a 24-h period. Statistically significant circadian variations were found in both melatonin and leptin profiles. Their relationship was inverse, i.e. when melatonin was high in the serum, leptin was comparably low. These results suggest that there is a rhythm in leptin levels in the adult male Syrian hamster and this rhythm is pineal gland (melatonin) and/or photoperiod dependent.     

Effect of melatonin implants on gonadal weights and pineal gland fine structure of the golden hamster

Weekly subcutaneous implants of melatonin in a beeswax pellet prevented the testicular regression which normally occurs in hamsters exposed to short photoperiod for 8 weeks. Normal (14L:10D) hamster testes were indistinguishable from the testes of melatonin-treated (1L:23D) hamsters. The exogenous melatonin had varied effects on the fine structure of the golden hamster pineal gland. Pinealocyte nuclear characteristics of melatonin-treated hamsters (smaller average diameter, less polymorphism, and more heterochromatin) as well as apparent reductions in the amounts of hypertrophic SER and lipid moieties seemed to indicate that melatonin caused inhibition of pineal gland activity, and in this respect counteracted the effects of short photoperiod. However, an apparent increase in the number of large mitochondria, membrane whorls and dense-cored secretory vesicles in pinealocytes of melatonin-treated hamsters suggests enhanced pineal gland activity.     

No evidence for extraocular photoreceptors in the circadian system of the Syrian hamster.

Campbell and Murphy reported recently that 3 h of bright light (13,000 lux) exposure to the area behind the knee caused phase shifts of the circadian rhythms of both body temperature and saliva melatonin in humans. The authors tested the hypothesis that extraocular photoreception is also involved in the circadian system of the Syrian hamster. Hamsters were bilaterally enucleated (eyes removed), and their backs were shaved. Hamsters with stable free-running rhythms in constant darkness were exposed to direct sunlight for 1 or 3 hours during their subjective night. Intact (control) animals showed phase shifts as expected, but the locomotor activity of enucleated animals was unaffected by the exposure to sunlight. The authors also measured the pineal melatonin content after exposure to sunlight. Pineal melatonin content in intact animals declined markedly as expected, but no decline was observed in the enucleated hamsters. The authors conclude that extraocular phototransduction is not capable of shifting the phase of the hamster's locomotor activity rhythm or of suppressing pineal melatonin synthesis.     

Maternal transfer of photoperiodic information in Siberian hamsters. III. Melatonin injections program postnatal reproductive development expressed in constant light

In Siberian hamsters, transference of photoperiodic information from dam to fetus influences pubertal testicular development of the young when reared either in constant light (LL) or postnatal photoperiods of intermediate length (i.e. 14L:10D). The effects of short photoperiods during gestation can be mimicked by administering melatonin to pregnant females. This experiment examined whether there exists a daily pattern of sensitivity to melatonin when it is administered to pineal-intact pregnant females housed on a long photoperiod. Groups of pregnant and lactating females received melatonin at each hour of the day. The young were not treated with exogenous melatonin. At the approximate time of maturation of their endogenous pineal melatonin rhythm (Day 15), the young were placed in LL to suppress pineal melatonin secretion. Young males were killed at 28 days of age. Afternoon (1200 h-2000 h) and late night (0400 h) injections of melatonin into females caused their male young to develop as though gestation occurred on a short photoperiod. Melatonin injections at other times were ineffective. The daily pattern of effectiveness of exogenous melatonin administration to pregnant females resembles that observed in adult males of this and other hamster species and is consistent with the hypothesis that a daily rhythm in sensitivity to melatonin is involved in the transduction of photoperiodic signals.     

Evidence that olfactory bulbectomy does not influence testicular regression in golden hamsters on short photoperiod by altering pineal melatonin production

Summary A recent study has shown that olfactory bulbectomy (BX) will prevent reproductive regression associated with short photoperiod in male golden hamsters. The results of experiments reported in this paper show that bulbectomized hamsters on long or short photoperiod still show a large nocturnal elevation in pineal melatonin production and that BX inhibits the reproductive regression induced by exogenous melatonin in pinealectomized hamsters. The data therefore indicate that BX does not inhibit short photoperiod induced testicular regression by altering melatonin secretion.     

Influences of the paraventricular and suprachiasmatic nuclei and olfactory bulbs on melatonin responses in the golden hamster

Removal of the pineal, or denervation of this gland by superior cervical ganglionectomy, blocks testicular regression in golden hamsters exposed to short photoperiods. Aspiration of the olfactory bulbs or lesions of the suprachiasmatic or paraventricular nuclei of the hypothalamus (SCNx or PVNx) have similar effects. We have examined the effects of these operations on pineal melatonin content and gonadal responses to various patterns of exogenous melatonin in order to examine the roles played by the olfactory bulbs, the SCN, and the PVN in hamster photoperiodism. SCNx and PVNx significantly reduced pineal melatonin content throughout the dark phase, while bulbectomy did not significantly affect melatonin concentrations at the time of the nocturnal peak. Bulbectomy significantly delayed the nightly onset of locomotor activity in hamsters exposed to 14L:10D, but not that of animals housed in 10L:14D. Although bulbectomy reduced the gonadal response to one or three daily injections of melatonin, these individuals exhibited significant testicular regression in response to melatonin as long as injections fell in the evening. In contrast, destruction of the PVN rendered hamsters unresponsive to one daily melatonin injection, but equally responsive to three injections, regardless of the time of day at which these injections were given. Whereas exposure of bulbectomized hamsters to 30 weeks of short days made them refractory to subsequent melatonin challenge, PVNx hamsters remained sensitive to appropriately timed melatonin treatments regardless of their photoperiodic history. Many, but not all hamsters that experienced complete SCN lesions remained sensitive to three daily melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Static and extremely low frequency electromagnetic field exposure: Reported effects on the circadian production of melatonin

The circadian rhythm of melatonin production (high melatonin levels at night and low during the day) in the mammalian pineal gland is modified by visible portions of the electromagnetic spectrum, i.e., light, and reportedly by extremely low frequency (ELF) electromagnetic fields as well as by static magnetic field exposure. Both light and non-visible electromagnetic field exposure at night depress the conversion of serotonin (5HT) to melatonin within the pineal gland. Several reports over the last decade showed that the chronic exposure of rats to a 60 Hz electric field, over a range of field strengths, severely attenuated the nighttime rise in pineal melatonin production; however, more recent studies have not confirmed this initial observation. Sinusoidal magnetic field exposure also has been shown to interfere with the nocturnal melatonin forming ability of the pineal gland although the number of studies using these field exposures is small. On the other hand, static magnetic fields have been repeatedly shown to perturb the circadian melatonin rhythm. The field strengths in these studies were almost always in the geomagnetic range (0.2 to 0.7 Gauss or 20 to 70 μtesla) and most often the experimental animals were subjected either to a partial rotation or to a total inversion of the horizontal component of the geomagnetic field. These experiments showed that several parameters in the indole cascade in the pineal gland are modified by these field exposures; thus, pineal cyclic AMP levels, N-acetyltransferase (NAT) activity (the rate limiting enzyme in pineal melatonin production), hydroxyindole-O-methyltransferase (HIOMT) activity (the melatonin forming enzyme), and pineal and blood melatonin concentrations were depressed in various studies. Likewise, increases in pineal levels of 5HT and 5-hydroxyindole acetic acid (5HIAA) were also seen in these glands; these increases are consistent with a depressed melatonin synthesis. The mechanisms whereby non-visible electromagnetic fields influence the melatonin forming ability of the pineal gland remain unknown; however, the retinas in particular have been theorized to serve as magnetoreceptors with the altered melatonin cycle being a consequence of a disturbance in the neural biological clock, i.e., the suprachiasmatic nuclei (SCN) of the hypothalamus, which generates the circadian melatonin rhythm. The disturbances in pineal melatonin production induced by either light exposure or non-visible electromagnetic field exposure at night appear to be the same but whether the underlying mechanisms are similar remains unknown.     

Melatonin-pineal relationships in female golden hamsters.

Light deprivation by blinding in female hamsters was followed by a regression of the reproductive organs, an elevation of pituitary LH concentration and a depression of pituitary prolactin levels. Pinealectomy negated almost completely the effects of light deprivation on the neuroendocrine-reproductive axis. Weekly subcutaneous implants of a melatonin:beeswax pellet completely prevented the pineal gland from inhibiting reproductive physiology in blinded hamsters. The findings suggest that melatonin is not pineal antigonadotrophic factor in female golden hamsters. Melatonin implanted hamsters also had higher than normal levels of plasma prolactin.     

Circadian regulation of pineal melatonin and reproduction in the Djungarian hamster

Gonadal state, pineal melatonin rhythms, and locomotor activity rhythms were examined in juvenile male Djungarian hamsters exposed to non-24-hr light cycles ("T-cycles") or to full photoperiods. At the end of 1 month, hamsters exposed to a 1-hr pulse of light every 24.33 hr (T 24.33) exhibited small testes, whereas those receiving the same amount of light every 24.78 hr (T 24.78) displayed stimulated gonads, ten-fold larger in size. Accompanying the nonstimulatory effect of the T 24.33 cycle were nocturnal peaks in both pineal melatonin content and serum melatonin concentration which were longer by approximately 4 hr than those observed on the photostimulatory T 24.78 cycle. Exposure to an intermediate-length T-cycle (T 24.53) resulted in a mixed gonadal response and in pineal and serum melatonin peaks of intermediate duration. Wheel-running activity was entrained to the T-cycles such that light was present only near the beginning of the subjective night, its phase (relative to activity onset) differing only slightly among T-cycle groups. Hence the durational differences observed in the melatonin peaks were apparently not due to the acute suppressive or phase-advancing effects of morning light on melatonin biosynthesis, but were rather the result of differences in the endogenous control of pineal activity by the circadian pacemaker system. While no strong correlation was detected between gonadal state and the phase of locomotor activity onset relative to the light pulse, a significant correlation was observed between gonadal state and the duration of daily locomotor activity (alpha). These data were compared to similar measures obtained from hamsters exposed to long-versus short-day full photoperiods (LD 16:8 vs. LD 10:14). In summary, the results of this study indicate involvement of the circadian pacemaker system of Djungarian hamsters in the control of pineal melatonin synthesis and secretion, and in photoperiodic time measurement. Furthermore, these data strengthen the hypothesis that it is the duration of nocturnal pineal melatonin secretion that is the critical feature of this neuroendocrine gland's photoperiodic signal.     

Diurnal Variations in Cyclic AMP and Melatonin Content of Golden Hamster Retina

Abstract: The diurnal variations and photic regulation of cyclic AMP and melatonin content in golden hamster retina were studied. Both parameters showed significant diurnal variations with maximal values at night. Light exposure during the night inhibited retinal cyclic AMP and melatonin levels, whereas exposure to darkness during the day significantly increased cyclic AMP and melatonin content. Incubation with melatonin of retinas excised at different intervals indicated that the methoxyindole inhibited cyclic AMP accumulation in a time-dependent manner. The inhibitory effect of melatonin at 2400 h and at noon showed a threshold concentration of 1 and 10 pM, respectively. At 0400 h melatonin did not affect cyclic AMP accumulation. The results indicate a diurnal variability of retinal cyclic AMP and melatonin content in hamsters, mainly influenced by a photic stimulus. Cyclic AMP could be a putative second messenger for melatonin action in golden hamster retina.     

Experimentally-induced diabetes reduces nocturnal pineal melatonin content in the Syrian hamster

Male, Syrian hamsters were rendered diabetic by either alloxan (60 mg/kg, i.v.) or streptozotocin (65 mg/kg, i.p.). Diabetic animals had reduced pineal melatonin contents during the night. Basal daytime values were not significantly altered. Diabetes may decrease melatonin synthesis by reducing the availability of glucose for metabolism or by decreasing the transport of tryptophan into pinealocytes for the synthesis of melatonin.     

Proteomic analysis of day-night variations in protein levels in the rat pineal gland

The pineal gland secretes the hormone melatonin. This secretion exhibits a circadian rhythm with a zenith during night and a nadir during day. We have performed proteome analysis of the superficial pineal gland in rats during daytime and nighttime. The proteins were extracted and subjected to 2-DE. Of 1747 protein spots revealed by electrophoresis, densitometric analysis showed the up-regulation of 25 proteins during nighttime and of 35 proteins during daytime. Thirty-seven of the proteins were identified by MALDI-TOF MS. The proteins up-regulated during the night are involved in the Krebs cycle, energy transduction, calcium binding, and intracellular transport. During the daytime, enzymes involved in glycolysis, electron transport, and also the Krebs cycle were up-regulated as well as proteins taking part in RNA binding and RNA processing. Our data show a prominent day-night variation of the protein levels in the rat pineal gland. Some proteins are up-regulated during the night concomitant with the melatonin secretion of the gland. Other proteins are up-regulated during the day indicating a pineal metabolism not related to the melatonin synthesis.     

The daily melatonin pattern in Djungarian hamsters depends on the circadian phenotype

Djungarian hamsters (Phodopus sungorus) bred at the Institute of Halle reveal three different circadian phenotypes. The wild type (WT) shows normal locomotor activity patterns, whereas in hamsters of the DAO (delayed activity onset) type, the activity onset is continuously delayed. Since the activity offset in those hamsters remains coupled to "light-on," the activity time becomes compressed. Hamsters of the AR (arrhythmic) type are episodically active throughout the 24 h. Previous studies showed that a disturbed interaction of the circadian system with the light-dark (LD) cycle contributes to the phenomenon observed in DAO hamsters. To gain better insight into the underlying mechanisms, the authors investigated the daily melatonin rhythm, as it is a reliable marker of the circadian clock. Hamsters were kept individually under standardized laboratory conditions (LD 14:10, T=22°C±2°C, food and water ad libitum). WT, DAO (with exactly 5 h delay of activity onset), and AR hamsters were used for pineal melatonin and urinary 6-sulfatoxymelatonin (aMT6s) measurement. Pineal melatonin content was determined at 3 time points: 4 h after "light-off" [D+4], 1 h before "light-on" [L-1], and 1h after "light-on" [L+1]). The 24-h profile of melatonin secretion was investigated by transferring the animals to metabolic cages for 27?h to collect urine at 3-h intervals for aMT6s analysis. WT hamsters showed high pineal melatonin content during the dark time (D+4, L-1), which significantly decreased at the beginning of the light period (L+1). In contrast, DAO hamsters displayed low melatonin levels during the part of the dark period when animals were still resting (D+4). At the end of the dark period (L-1), melatonin content increased significantly and declined again when light was switched on (L+1). AR hamsters showed low melatonin levels, comparable to daytime values, at all 3 time points. The results were confirmed by aMT6s data. WT hamsters showed a marked circadian pattern of aMT6s excretion. The concentration started to increase 3?h after "light-off" and reached daytime values 5 h after "light-on." In DAO hamsters, in contrast, aMT6s excretion started about 6?h later and reached significantly lower levels compared to WT hamsters. In AR animals, aMT6s excretion was low at all times. The results clearly indicate the rhythm of melatonin secretion in DAO hamsters is delayed in accord with their delayed activity onset, whereas AR hamsters display no melatonin rhythm at all. Since the regulatory pathways for the rhythms of locomotor activity and melatonin synthesis (which are downstream from the suprachiasmatic nucleus [SCN]) are different but obviously convey the same signal, we conclude that the origin of the phenomenon observed in DAO hamsters must be located upstream of the SCN, or in the SCN itself.     

Maintenance of testicular function in Turkish hamsters: interaction of photoperiod and the pineal gland

Adult male Turkish hamsters maintained testicular function when exposed to photoperiods of 15, 16, or 17 h of light per day. Photoperiods of less than 15 or greater than 17 h of light per day induced a rapid and complete testicular regression. As pinealectomy had been shown by others to induce testicular regression in long-day Turkish hamsters, we thought that regression on 18 or more h of light might be based on the inability of the pineal to generate a daily rhythm of melatonin in production and release. This proved not to be the case. Animals exposed to 14-18 and 20 h of light per day had a robust nocturnal melatonin rhythm.     

冬眠哺乳动物心血管机能特点

冬眠动物心血管系统适应于冬眠和激醒过程的特殊生理条件形成了其显著的机能稳定性。我们在总结已有研究的基础提出了冬眠动物心血管系统具有耐低体温,抗主律失常,耐缺氧三大机能特点。这些特点不仅是冬眠动物五非冬眠动物的区别,也是冬眠动物在冬眠季机能强化的方面。     

Nocturnal increase in the sensitivity of the Syrian hamster pineal gland to isoproterenol is darkness dependent

The sensitivity of the Syrian hamster pineal gland to stimulation by isoproterenol is greatly increased in the latter half of the daily dark phase. This increased sensitivity requires a period of dark exposure for up to 6.5 hr. Also, if dark-maintained hamsters are exposed to light in the latter half of the night pineal melatonin levels drop precipitously but can be restimulated by isoproterenol administration. As the interval of light exposure continues, however, the pineal sensitivity to isoproterenol decreases.