Effect of a melatonin implant on the circadian variation of plasma prolactin and rectal temperature in newborn sheep.

Plasma prolactin and rectal temperature show a circadian rhythm in newborn sheep raised under continuous light. Melatonin lowers the concentration of plasma prolactin but it is not known if it affects its circadian rhythm. To detect whether melatonin acts on the circadian system we studied the effect of a subcutaneous melatonin implant in the circadian rhythms of prolactin and rectal temperature in newborn lambs raised under continuous light. We placed catheters in the pedal artery and vein in 9 newborn lambs (2-5 days of age). A subcutaneous melatonin implant was placed in 4 of the lambs at 9-12 days of age. Blood samples and rectal temperature measurements were obtained hourly for a period of 24 h, 11-15 days after the implant, at 20-27 days of age. To avoid interferences of heparin in our melatonin assay, serum melatonin concentration was measured before and during the implant in three additional newborns. Prolactin and melatonin were measured by RIA. Melatonin concentrations were 52.8 +/- 45.9 pg/ml (day) and 315.5 +/- 77.0 pg/ml (night) before treatment (SEM, P less than 0.001), and increased to 594.1 +/- 54.5 pg/ml after placing the implant (there was no difference in melatonin concentration between day and night during the time that the implant was in place). Melatonin had no effect on rectal temperature or its rhythm, but decreased basal plasma prolactin concentration (control: 97.5 +/- 11.3 ng/ml; treated: 25.1 +/- 2.4 ng/ml, P less than 0.001) and abolished the prolactin circadian rhythm, (Cosinor analysis): control: log prolactin (ng/ml) = 1.8 + 0.26 cos 15 (t - 11.16), p = 0.05; treated: log prolactin (ng/ml) = 1.2 + 0.14 cos 15 (t - 9.43), P = 0.36.     

Circadian rhythm of aldosterone in dairy cattle during the summer

Twelve Holstein heifers, pregnant from 120–150 days were used to study the circadian rhythm of aldosterone, cortisol, progesterone, sodium and potassium in dairy cattle during the summer in Louisiana. Cortisol was not significantly influenced by time (time 1 = 06.00 h). Aldosterone, sodium, potassium and progesterone changed significantly (P<.01) with time. Aldosterone peaked (116.5±17.2 pg/ml) at 08.00 h and then generally declined to 16.00 h (26.7±2.0 pg/ml). Sodium generally increased from 06.00 h (320.1±7.3 mg%) to 18.00 h (377.9±6.1 mg%), and then declined. Potassium generally increased from 06.00 h (20.9±0.5 mg%) to 22.00 h (23.0±0.3 mg%). Progesterone generally increased from 07.00 h (2.8±0.4 mg/ml) to 24.00 h (7.5±1.4 mg/ml). Aldosterone was significantly related to temperature associated with the time of the day samples were taken (r = 0.66, P<.02).     

Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction

AIMS: Atherosclerosis is a chronic disease that, from its origin to its ultimate complications, involves inflammatory cells, inflammatory proteins, and inflammatory responses from vascular cells. It has been demonstrated that cytokine activities are under neuroendocrine control, in part exerted by the pineal gland through the circadian secretion of its main product melatonin. Melatonin is mainly released during the night, but the precise relationship between melatonin and the light/dark rhythm of interleukin-6 in patients with acute myocardial infarction is still unclear. METHODS AND RESULTS: The study included 60 patients diagnosed with acute myocardial infarction and 60 healthy volunteers whose venous blood samples were collected at 09:00 h (light period) and 02:00 h (dark period). Our results demonstrate that interleukin-6 concentrations presented a light/dark pattern with mean serum concentrations being higher in the acute myocardial infarction group than in the control group (101.26 +/- 13.43 and 52.67 +/- 7.73 pg/ml at 02:00 h, 41.93 +/- 5.90 and 22.98 +/- 4.49 pg/ml at 09:00 h, respectively, p < 0.05). Differences in the day/night changes in melatonin levels in control subjects (48.19 +/- 7.82 at 02:00 h, 14.51+/- 2.36 at 09:00 h, pg/ml) and acute myocardial infarction patients (25.97 +/- 3.90 at 02:00 h, 12.29 +/- 4.01 at 09:00 h, pg/ml) (p < 0.05) were a result of a reduced nocturnal elevation of melatonin in the acute myocardial infarction group. CONCLUSIONS: The current findings suggest that the circadian secretion of melatonin may be responsible at least in part for light/dark variations of endogenous interleukin-6 production in patients with acute myocardial infarction. In this study, the melatonin seems to have an anti-inflammatory effect.     

A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure

Night shift work is associated with a myriad of health and safety risks. Phase‐shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a “snapshot” of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (～3500 lux; ～1100 µW/cm²) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths—especially short wavelengths (“blue‐blockers”)—while traveling home after the shifts, and sleep in the dark (08:30–15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (T_min), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The T_min of the experimental subjects (n=11) was 04:24±0.8 h (mean±SD) at baseline and 7:36±1.4 h after the night shifts. Thus, after two night shifts, the T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min of the control subjects (n=12) was 04:00±1.2 h at baseline and drifted to 4:36±1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Human Melatonin and Cortisol Circadian Rhythms in Patients with Coronary Heart Disease

Cortisol and melatonin have well known circadian rhythms, coupled to the solar day. Melatonin has been shown to serve as an endogenuous “Zeitgeber” (time giver) and is secreted by the human pineal gland throughout the night but not during the day. Patients with coronary heart disease (CHD) have significant depressed nocturnal melatonin secretion compared to healthy individuals (Brugger et al., 1995). In addition to our previous study we measured serum concentrations of cortisol to evaluate whether the circadian rhythm of cortisol secretion is also different in patients with CHD. Blood was collected by venous puncture at 0200 and at 1400, serum separated and kept frozen at -20°C until analysis. Cortisol and melatonin were measured with a commercially available radioimmunoassay according to the instructions of the manufacturer. Nineteen patients with angiographically documented CHD (mean age 53 years) participated in this study. As control group served 12 adults without any signs of CHD. Melatonin serum concentrations (median; mean ± SD) at night were significantly depressed in patients with coronary heart disease (7.8; 8.6 ± 3.3 pg/ml) in comparison to the control group (38.0; 45.4 ± 24.1 pg/ml) p &lt; 0.01. Melatonin in the afternoon was not detectable in either of the groups. Cortisol values at night were significantly raised in patients with coronary heart disease (6.0; 7.2 ± 3.7 µg/dl) in comparison to the control group (2.7; 3.8 ± 2.9 µg/dl) p &lt; 0.05. Cortisol levels in the afternoon were also elevated in patients with CHD (8.9; 9.5 ± 3.8 µg/dl) but there was no significant difference compared to controls (6.8; 6.9 ± 4.5 µg/dl). The results of the present study indicate that patients with coronary heart disease have atypical secretory patterns of nocturnal cortisol and melatonin secretion.     

Influence of Light Intensity on Plasma Melatonin and Locomotor Activity Rhythms in Tench

Melatonin production by the pineal organ is influenced by light intensity, as has been described in most vertebrate species, in which melatonin is considered a synchronizer of circadian rhythms. In tench, strict nocturnal activity rhythms have been described, although the role of melatonin has not been clarified. In this study we investigated daily activity and melatonin rhythms under 12∶12 light‐dark (LD) conditions with two different light intensities (58.6 and 1,091 µW/cm²), and the effect of 1 h broad spectrum white light pulses of different intensities (3.3, 5.3, 10.5, 1,091.4 µW/cm²) applied at middarkness (MD) on nocturnal circulating melatonin. The results showed that plasma melatonin in tench under LD 12∶12 and high light conditions displayed rhythmic variation, where values at MD (255.8±65.9 pg/ml) were higher than at midlight (ML) (70.7±31.9 pg/ml). Such a difference between MD and ML values was reduced in animals exposed to LD 12∶12 and low light intensity. The application of 1 h light pulses at MD lowered plasma melatonin to 111.6±3.2 pg/ml (in the 3.3–10.5 µW/cm² range) and to 61.8±18.3 pg/ml (with the 1,091.4 µW/cm² light pulse) and totally suppressed nocturnal locomotor activity. These results show that melatonin rhythms persisted in tench exposed to low light intensity although the amplitude of the rhythm is affected. In addition, it was observed that light pulses applied at MD affected plasma melatonin content and locomotor activity. Such a low threshold suggests that the melatonin system is capable of transducing light even under dim conditions, which may be used by this nocturnal fish to synchronize to weak night light signals (e.g., moonlight cycles).     

THE EFFECTS OF SKIN PRESSURE BY CLOTHING ON CIRCADIAN RHYTHMS OF CORE TEMPERATURE AND SALIVARY MELATONIN

The present experiment investigated the effects of skin pressure by foundation garments (girdle and brassiere) on the circadian rhythms of core temperature and salivary melatonin. Ten healthy females (18–23 years) maintained regular sleep-wake cycles for a week prior to participation in the experiment. The experiments were performed from June to August 1999 using a bioclimatic chamber controlled at 26.5°C ± 0.2°C and 62% ± 3% RH. Ambient light intensity was controlled at 500 lux from 07:30 to 17:30, 100 lux from 17:30 to 19:30, 20 lux from 19:30 to 23:30; there was total darkness from 23:30 to 07:30. The experiment lasted for 58h over three nights. The participants arose at 07:30 on the first full day and retired at 23:30, adhering to a set schedule for 24h, but without wearing foundation garments. For the final 24h of the second full day, the subjects wore foundation garments. Rectal and leg skin temperatures were measured continuously throughout the experiment. Saliva and urine were collected every 4h for the analysis of melatonin and catecholamines, respectively. Skin pressure applied by the foundation garments was in the range 11–17 gf/cm² at the regions of the abdomen, hip, chest, and back. The main results were as follows: (1) Rectal temperatures were significantly higher throughout the day and night when wearing foundation garments. (2) The nocturnal level of salivary melatonin measured at 03:30 was 115.2 ± 40.4 pg/mL (mean ± SEM, N = 10) without and 51.3 ± 18.4 pg/mL (mean ± SEM, N = 10) with foundation garments. (3) Mean urinary noradrenaline excretion was significantly lower throughout the day and night when wearing foundation garments (p <. 05), but mean urinary adrenaline excretion was not different. The results suggest that skin pressure by clothing could markedly suppress the nocturnal elevation of salivary melatonin, resulting in an increase of rectal temperature. (Chronobiology International, 17(6) 783–793, 2000)     

Relationship of atypical melatonin rhythm with two circadian clock outputs in B6D2F(1) mice

Circadian rhythms in body temperature, locomotor activity, and the circadian changes of plasma and pineal melatonin content were investigated in B6D2F(1) mice synchronized by 12 h of light and 12 h of darkness. During 8 wk continuous recording, activity and temperature displayed a marked stable and reproducible circadian rhythm, with both peaks occurring near the middle of darkness. Both 24- and 12-h rhythmic components were also significantly detected. Mean plasma melatonin concentration rose steadily during the light span and reached a maximum (30.6 +/- 10.0 pg/ml) at 11 h after light onset (HALO), then gradually decreased after the onset of darkness to a nadir (4.7 +/- 0.4 pg/ml) at 20 HALO. Mean pineal content followed a pattern parallel to that of plasma concentration (peak at 11 HALO: 17.7 +/- 1.0 pg/gland; trough at 17 HALO: 4.7 +/- 1.0 pg/gland). In addition, a second sharp peak was observed at 21 HALO (20.2 +/- 3.5 pg/gland). Plasma and pineal contents displayed large and statistically significant circadian changes, with a composite rhythm of period (24 + 12 h). This mouse model has predominant production and secretion of melatonin during the day. This possibly contributes to a similar coupling between chronopharmacology mechanisms and the rest-activity cycle in these mice and in human subjects.     

Circadian Phase,Sleepiness, and Light Exposure Assessment in Night Workers With and Without Shift Work Disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean?±?SD] age: 39.2?±?12.5 yrs; mean yrs on shift?=?9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6?±?8.6 yrs; mean years on shift?=?8.4) participated. All participants were admitted to the sleep center at 16:00?h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00?h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42?±?3.25?h, whereas in the SWD group it was 20:42?±?2.21?h (z = 2.4; p?<?.05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00–09:00?h) was significantly shorter (3.6?±?.90?min: [M?±?SEM]) in the SWD group compared with that in ANW group (6.8?±?.93?min). DLMO was significantly correlated with insomnia severity (r = ?.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00?h) as than ANW ones (798 vs. 180 lux [M?±?SD], respectively z?=??1.7; p?<?.05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule. (Author correspondence: vgumeny1@hfhs.org)     

Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions

Conflicting evidence exists as to whether there are differences between males and females in circadian timing. The aim of the current study was to assess whether sex differences are present in the circadian regulation of melatonin and cortisol in plasma and urine matrices during a constant routine protocol. Thirty-two healthy individuals (16 females taking the oral contraceptive pill (OCP)), aged 23.8 ± 3.7 (mean ± SD) years, participated. Blood (hourly) and urine (4-hourly) samples were collected for measurement of plasma melatonin and cortisol, and urinary 6-sulfatoxymelatonin (aMT6s) and cortisol, respectively. Data from 28 individuals (14 females) showed no significant differences in the timing of plasma and urinary circadian phase markers between sexes. Females, however, exhibited significantly greater levels of plasma melatonin and cortisol than males (AUC melatonin: 937 ± 104 (mean ± SEM) vs. 642 ± 47 pg/ml.h; AUC cortisol: 13581 ± 1313 vs. 7340 ± 368 mmol/L.h). Females also exhibited a significantly higher amplitude rhythm in both hormones (melatonin: 43.8 ± 5.8 vs. 29.9 ± 2.3 pg/ml; cortisol: 241.7 ± 23.1 vs. 161.8 ± 15.9 mmol/L). Males excreted significantly more urinary cortisol than females during the CR (519.5 ± 63.8 vs. 349.2 ± 39.3 mol) but aMT6s levels did not differ between sexes. It was not possible to distinguish whether the elevated plasma melatonin and cortisol levels observed in females resulted from innate sex differences or the OCP affecting the synthetic and metabolic pathways of these hormones. The fact that the sex differences observed in total plasma concentrations for melatonin and cortisol were not reproduced in the urinary markers challenges their use as a proxy for plasma levels in circadian research, especially in OCP users.     

Melatonin Binding Sites in Senegal Sole: Day/Night Changes in Density and Location in Different Regions of the Brain

We localized melatonin binding sites in different brain regions (optic tectum, telencephalon, cerebellum, hypothalamus, olfactory bulbs, and medulla oblongata) of Senegal sole, a species of aquaculture interest, and checked day/night changes in density (B_max) at mid‐light (ZT06) and mid‐dark (ZT18). Plasma melatonin was measured using a radioimmunoassay, while binding assays were performed using 2‐[¹²⁵I]iodomelatonin as a radioligand. Plasma melatonin concentrations were significantly lower at mid‐light (189.5±46 pg/ml) than mid‐dark (455.5±163 pg/ml). Values of B_max were statistically significantly higher in the optic tectum (5.6±0.6 and 12.3±1 fmol/mg prot, at mid‐light and mid‐dark, respectively) and in the cerebellum (7.7±1.1 and 10.6±1.3 fmol/mg prot, at mid‐light and mid‐dark, respectively). Significant day/night differences were only observed in these two tissues. These results show for the first time the distribution of melatonin binding sites within the brain of a flatfish species and their lack of down‐regulation.     

Evidence that 19-hydroxyandrostenedione is secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system in man

Plasma 19-hydroxyandrostenedione (19-OH-A-dione) concentrations in man were evaluated using a specific and sensitive radioimmunoassay. Plasma 19-OH-A-dione concentrations (mean ± SE) in normal subjects are 151 ± 14 pg/ml (n=13) in males and 141 ± 9 pg/ml (n=14) in females. Plasma 19-OH-A-dione (mean ± SE) rises significantly during ACTH stimulation (116 ± 25 pg/ml vs 288 ± 38 pg/ml; P<0.01; n=5), declines significantly during dexamethasone suppression (180 ± 30 pg/ml vs 36 ± 14 pg/ml; P<0.01; n=4) and rises significantly during angiotensin II infusion (89 ± 10 pg/ml vs 159 ± 27 pg/ml; P<0.05; n=5). Plasma 19-OH-A-dione in the adrenal vein is much higher than that in the inferior vena cava (2076–3076 pg/ml vs 115–184 pg/ml; n=2). These results demonstrate that 19-OH-A-dione is directly secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system.     

Coccidioides posadasii infection alters the expression of pulmonary surfactant proteins (SP)-A and SP-D

Background

Patients with asthma demonstrate circadian variations in the airway inflammation and lung function. Pinealectomy reduces the total inflammatory cell number in the asthmatic rat lung. We hypothesize that melatonin, a circadian rhythm regulator, may modulate the circadian inflammatory variations in asthma by stimulating the chemotaxins expression in the lung epithelial cell.

Methods

Lung epithelial cells (A549) were stimulated with melatonin in the presence or absence of TNF-α(100 ng/ml). RANTES (Regulated on Activation Normal T-cells Expressed and Secreted) and eotaxin expression were measured using ELISA and real-time RT-PCR, eosinophil chemotactic activity (ECA) released by A549 was measured by eosinophil chemotaxis assay.

Results

TNF-α increased the expression of RANTES (307.84 ± 33.56 versus 207.64 ± 31.27 pg/ml of control, p = 0.025) and eotaxin (108.97 ± 10.87 versus 54.00 ± 5.29 pg/ml of control, p = 0.041). Melatonin(10^-10 to 10^-6M) alone didn't change the expression of RNATES (204.97 ± 32.56 pg/ml) and eotaxin (55.28 ± 6.71 pg/ml). However, In the presence of TNF-α (100 ng/ml), melatonin promoted RANTES (410.88 ± 52.03, 483.60 ± 55.37, 559.92 ± 75.70, 688.42 ± 95.32, 766.39 ± 101.53 pg/ml, treated with 10^-10, 10^-9, 10^-8, 10^-7,10^-6M melatonin, respectively) and eotaxin (151.95 ± 13.88, 238.79 ± 16.81, 361.62 ± 36.91, 393.66 ± 44.89, 494.34 ± 100.95 pg/ml, treated with 10^-10, 10^-9, 10^-8, 10^-7, 10^-6M melatonin, respectively) expression in a dose dependent manner in A549 cells (compared with TNF-α alone, P < 0.05). The increased release of RANTES and eotaxin in A549 cells by above treatment were further confirmed by both real-time RT-PCR and the ECA assay.

Conclusion

Taken together, our results suggested that melatonin might synergize with pro-inflammatory cytokines to modulate the asthma airway inflammation through promoting the expression of chemotaxins in lung epithelial cell.     

Melatonin production and light exposure of rotating night workers

Decreased melatonin production, due to acute suppression of pineal melatonin secretion by light exposure during night work, has been suggested to underlie higher cancer risks associated with prolonged experience of night work. However, the association between light exposure and melatonin production has never been measured in the field. In this study, 24-h melatonin production and ambulatory light exposure were assessed during both night-shift and day/evening-shift periods in 13 full-time rotating shiftworkers. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s), and light exposure was measured with an ambulatory photometer. There was no difference in total 24-h aMT6s excretion between the two work periods. The night-shift period was characterized by a desynchrony between melatonin and sleep-wake rhythms, as shown by higher melatonin production during work and lower melatonin production during sleep when working night shifts than when working day/evening shifts. Light exposure during night work showed no correlation with aMT6s excreted during the night of work (p?>?.5), or with the difference in 24-h aMT6s excretion between the two work periods (p >?.1). However, light exposure during night work was negatively correlated with total 24-h aMT6s excretion over the entire night-shift period (p?相似文献   

Melatonin and Human Rhythms

Melatonin signals time of day and time of year in mammals by virtue of its pattern of secretion, which defines 'biological night.' It is supremely important for research on the physiology and pathology of the human biological clock. Light suppresses melatonin secretion at night using pathways involved in circadian photoreception. The melatonin rhythm (as evidenced by its profile in plasma, saliva, or its major metabolite, 6-sulphatoxymelatonin [aMT6s] in urine) is the best peripheral index of the timing of the human circadian pacemaker. Light suppression and phase-shifting of the melatonin 24 h profile enables the characterization of human circadian photoreception, and circulating concentrations of the hormone are used to investigate the general properties of the human circadian system in health and disease. Suppression of melatonin by light at night has been invoked as a possible influence on major disease risk as there is increasing evidence for its oncostatic effects. Exogenous melatonin acts as a 'chronobiotic.' Acutely, it increases sleep propensity during 'biological day.' These properties have led to successful treatments for serveal circadian rhythm disorders. Endogenous melatonin acts to reinforce the functioning of the human circadian system, probably in many ways. The future holds much promise for melatonin as a research tool and as a therapy for various conditions.     

Melatonin directly stimulates the secretion of progesterone by human and bovine granulosa cells in vitro

Melatonin, at concentrations and periods of exposure reflecting those present during the circadian cycle, was investigated for its influence on steroid production by granulosa cells cultured in serum-supplemented medium. At high (200 pg/ml) but not low (20 pg/ml) physiological concentrations, melatonin significantly stimulated progesterone production by human granulosa cells. This response was independent of the overall level of cell activity and was seen under the different culture conditions associated with different culture media. Exposure to melatonin for 8 h significantly stimulated progesterone secretion to a level similar to that achieved under continuous exposure, and the effect was reduced to control levels during subsequent periods in which no melatonin was added. Melatonin had no consistent effect on aromatase activity in the conversion of stored or serum-available androgen to oestradiol. Melatonin significantly stimulated progesterone production by bovine granulosa cells in vitro, at concentrations similar to those present during the endogenous nocturnal rise (100-400 pg/ml). This response to physiological conditions by human and bovine cells suggests a role for melatonin in the regulation of progesterone production by the ovary.     

Morning Melatonin Has Limited Benefit as a Soporific For Daytime Sleep After Night Work

Exogenous melatonin administration in humans is known to exert both chronobiotic (phase shifting) and soporific effects. In a previous study in our lab, young, healthy, subjects worked five consecutive simulated night shifts (23:00 to 07:00 h) and slept during the day (08:30 to 15:30 h). Large phase delays of various magnitudes were produced by the study interventions, which included bright light exposure during the night shifts, as assessed by the dim light melatonin onset (DLMO) before (baseline) and after (final) the five night shifts. Subjects also ingested either 1.8 mg sustained‐release melatonin or placebo before daytime sleep. Although melatonin at this time should delay the circadian clock, this previous study found that it did not increase the magnitude of phase delays. To determine whether melatonin had a soporific effect, we controlled the various magnitudes of phase delay produced by the other study interventions. Melatonin (n=18) and placebo (n=18) groups were formed by matching a melatonin participant with a placebo participant that had a similar baseline and final DLMO (±1 h). Sleep log measurements of total sleep time (TST) and actigraphic measurements of sleep latency, TST, and three movement indices for the two groups were examined. Although melatonin was associated with small improvements in sleep quality and quantity, the differences were not statistically significant by analysis of variance. However, binomial analysis indicated that melatonin participants were more likely to sleep better than their placebo counterparts on some days with some measures. It was concluded that, the soporific effect of melatonin is small when administered prior to 7 h daytime sleep periods following night shift work.     

Time of day and water temperature modify the physiological stress response in green sturgeon,Acipenser medirostris

The effects of time of day and water temperature on the acute physiological stress response were investigated in young-of-the-year green sturgeon (Acipenser medirostris). The response to a 1-min air-emersion stressor was assessed during the day (08.00 h) and at night (20.00 h), as well as after acclimation to either 11 degrees C or 19 degrees C. Blood samples were collected prior to stress and at several times after exposure to the stressor, and plasma concentrations of cortisol, lactate, and glucose were determined. The magnitudes of cortisol (19.1 ng ml(-1) vs. 4.9 ng ml(-1)) and lactate (190.6 mg l(-1) vs. 166.7 mg l(-1)) were significantly higher in fish stressed at night when compared with the day. There were no significant differences in glucose levels between time periods. Although, acclimation temperature did not affect peak cortisol concentrations (56.7 and 50.3 ng ml(-1) at 11 degrees C and 19 degrees C, respectively), the duration of the response was significantly extended at 11 degrees C. Post-stressor lactate increases were similar between temperature groups, but at 11 degrees C post-stressor glucose levels were significantly increased through 6 h, suggesting stressor-induced glycogenolysis and gluconeogenesis or decreased glucose utilization. These data demonstrate that the physiological stress response in green sturgeon is modified by both time of day and temperature.     

Melatonin and Human Rhythms

Melatonin signals time of day and time of year in mammals by virtue of its pattern of secretion, which defines ‘biological night.’ It is supremely important for research on the physiology and pathology of the human biological clock. Light suppresses melatonin secretion at night using pathways involved in circadian photoreception. The melatonin rhythm (as evidenced by its profile in plasma, saliva, or its major metabolite, 6‐sulphatoxymelatonin [aMT6s] in urine) is the best peripheral index of the timing of the human circadian pacemaker. Light suppression and phase‐shifting of the melatonin 24 h profile enables the characterization of human circadian photoreception, and circulating concentrations of the hormone are used to investigate the general properties of the human circadian system in health and disease. Suppression of melatonin by light at night has been invoked as a possible influence on major disease risk as there is increasing evidence for its oncostatic effects. Exogenous melatonin acts as a ‘chronobiotic.’ Acutely, it increases sleep propensity during ‘biological day.’ These properties have led to successful treatments for serveal circadian rhythm disorders. Endogenous melatonin acts to reinforce the functioning of the human circadian system, probably in many ways. The future holds much promise for melatonin as a research tool and as a therapy for various conditions.     

Melatonin and human rhythms

Melatonin signals time of day and time of year in mammals by virtue of its pattern of secretion, which defines 'biological night.' It is supremely important for research on the physiology and pathology of the human biological clock. Light suppresses melatonin secretion at night using pathways involved in circadian photoreception. The melatonin rhythm (as evidenced by its profile in plasma, saliva, or its major metabolite, 6-sulphatoxymelatonin [aMT6s] in urine) is the best peripheral index of the timing of the human circadian pacemaker. Light suppression and phase-shifting of the melatonin 24 h profile enables the characterization of human circadian photoreception, and circulating concentrations of the hormone are used to investigate the general properties of the human circadian system in health and disease. Suppression of melatonin by light at night has been invoked as a possible influence on major disease risk as there is increasing evidence for its oncostatic effects. Exogenous melatonin acts as a 'chronobiotic.' Acutely, it increases sleep propensity during 'biological day.' These properties have led to successful treatments for serveal circadian rhythm disorders. Endogenous melatonin acts to reinforce the functioning of the human circadian system, probably in many ways. The future holds much promise for melatonin as a research tool and as a therapy for various conditions.