Ontogeny of the circadian variation of plasma prolactin in sheep

The ontogeny of circadian rhythms is unknown. The newborn sheep has a circadian rhythm of temperature; to study the ontogeny of other rhythms, we examined the 24-h variation of plasma prolactin concentration in fetal and newborn sheep. To this effect, we measured plasma prolactin concentration in chronically catheterized fetuses (n = 7) and in newborn lambs raised under short day nycthemeral (12 light:12 dark, n = 13) or constant light conditions (n = 5). Indwelling catheters were implanted into the jugular vein and carotid artery of late gestation fetuses (0.9 gestation) and newborns (5-29 days old). Experiments were performed 4 or more days after surgery. Lambs were kept in a canvas sling and were fed cow's milk either by mouth or through a nasogastric catheter at established time intervals. Haematocrit, pH, and blood gases were measured before and after the experiments in all cases and remained within normal values. Lights were on and room temperature was maintained constant during the whole experiment. Samples were obtained every 1-2 h for 24 h in fetuses and newborn lambs under nycthemeral conditions and every hour for 48 h in newborn lambs kept under constant light. Plasma prolactin was measured by radioimmunoassay. The presence of a 24 h rhythm was determined by Cosinor analysis. Fetuses, aged 129 +/- 6 days (SD) n = 7, showed a variation in plasma prolactin concentration with a period of 24 h that fits the equation: plasma prolactin (ng ml-1) = 97.0 + 15.4 cos 15 (t-23.0), P = 0.035.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian variation of rectal temperature in newborn sheep

In adult animals, body temperature shows a 24 h rhythm that is endogenously generated. We examined the existence of 24 h rhythms of temperature in 10 newborn sheep. Four newborns, aged 5 to 28 days were kept with their mothers under nycthemeral conditions, and the remaining 6 lambs, aged 21 to 43 days, were kept with their mothers in constant light from day 3 after birth. Experiments were performed with both groups of lambs in the laboratory. Additional experiments were performed with the 6 lambs kept under constant light while they were in the pen with their mothers to rule out artifacts due to manipulation or artificial feeding. During the experiments done in the laboratory, the lambs were kept blindfolded in a canvas sling and were fed baby formula approximately every four hours (lambs kept under nycthemeral conditions) or every hour (constant light lambs). Lights were on in the room during the whole experiment. Temperature in the room was maintained at 18 +/- 0.1 degrees C (mean +/- SEM). In the experiments done in the pen, animals remained with the mother and room temperature was not controlled. In all experiments, rectal temperature was hourly measured for 24 h with a thermocouple inserted in the lamb's rectum and connected to a Philipp Schenk digital recorder. Lambs kept under nycthemeral conditions show a variation of mean rectal temperature (t degree) with a period of 24 h, that fits a cosine function (P less than 0.001): Rectal t degree (degree C) = 40.6 + 0.4 cos [15 (t-16.22)]. The mesor is 40.6, the amplitude 0.4, and the acrophase expressed in h is 16.22 (n = 4). Lambs kept under constant light show a variation of rectal temperature with a period of 24 h, independently of whether the measurements were done in the laboratory or in the pens. The acrophases varied widely in these animals, when the acrophase were synchronized so theta = 2400, mean rectal temperature showed a variation with a period of 24 h that fits the equation (P less than 0.001): Rectal t degree (degree C) = 39.5 + 0.18 cos [15 (t-0.23)]. The presence of a 24 h rhythm of rectal t degree in lambs kept under nycthemeral conditions, and its persistence in lambs kept under constant light suggests that the rhythm of rectal temperature observed in the newborn lamb is a true circadian rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of imipramine on the circadian rhythm of plasma melatonin in unipolar depression

The authors took a series of 20 serum samples over a 24-hr period for measurement of melatonin in four men and six women with Major Depressive Disorder (DSM-III), at baseline (depressed) and after 4 weeks on imipramine (150-200 mg/day) after achieving clinical remission. After successful treatment with imipramine, 24-hr secretion and peak levels of melatonin were significantly higher than at baseline, with no difference in time of peak level. Testing after 2 weeks of treatment (four subjects), with only a partial or no clinical response, revealed no differences compared with baseline. The therapeutic efficacy of imipramine may be associated with an enhancement of noradrenergic activity.     

Effect of rubidium on the course of illness and the circadian rectal temperature in a 66-year-old depressive woman

Rubidium (Rb+) has an antidepressive effect and shortens the circadian period in animals, whereas Li+, another alcalic metal, lengthens it. When we treated a depressive Li+ nonresponder with Rb+, we found an improvement of depression as well as a phase advance of the temperature rhythm in relation to the rest-activity rhythm.     

Effects of maintaining solstice light and temperature on reproductive activity, coat growth, plasma prolactin and melatonin in goats.

Interactive effects of light and temperature on aspects of seasonality were studied in female British Saanen dairy goats. Four groups of adult non-pregnant non-lactating goats (n = 5) were housed under the following conditions: controls (July-June): natural photoperiod and temperature; group 1 (July-December): long days (16 h light: 8 h dark) and natural temperature; group 2 (July-December): long days and average summer temperature (17.6 degrees C); group 3 (December-June): short days (8 h light: 16 h dark) and winter temperature (8.4 degrees C). Plasma prolactin and progesterone were measured once a week, circadian changes in prolactin and melatonin were determined in December and May, and coat development was assessed. Seasonal variation in prolactin was influenced by manipulation of both daylength and temperature. In group 1, prolactin concentrations decreased as the environmental temperature decreased, despite maintenance of long days. When light and temperature were maintained under summer (group 2) and winter (group 3) conditions, prolactin remained relatively constant, although at different high and low set points, respectively, but with indications of a seasonal rhythm. An asymptotic relationship between prolactin and temperature was maintained under all daylengths. The circadian pattern of melatonin was related to daylength and was not influenced significantly by temperature. Onset of oestrus was unaltered. In group 3 (maintained winter solstice light and temperature), anoestrus was delayed (P < 0.05) from a median control date of 17 March to a median date of 28 April. Winter coat development was delayed in group 1; group 2 showed premature moulting of the winter coat; and in group 3, development of the summer coat was delayed. The results imply that temperature modifies the influence of daylength on prolactin secretion and hair follicle growth by mechanisms that do not involve melatonin.     

The effect of pinealectomy on circadian plasma melatonin levels in house sparrows and European starlings.

We determined 24-hr plasma melatonin profiles in intact, sham-pinealectomized, and pinealectomized European starlings (Sturnus vulgaris) and house sparrows (Passer domesticus) in a light-dark (LD) cycle and in constant darkness (DD). In the intact and sham-pinealectomized birds of both species, a melatonin rhythm was found, with low levels during the day and high levels during the night. Pinealectomy abolished the nighttime peak of melatonin in both species; hence, levels were low at all times sampled. This uniform response of plasma melatonin to pinealectomy contrasts with the differential response of circadian activity rhythms to pinealectomy for these two species. In DD, locomotor activity in pinealectomized house sparrows is usually arrhythmic, whereas in starlings a rhythm usually persists. This suggests that in the latter species free-running circadian rhythms are not necessarily dependent on a rhythm in plasma melatonin. The same is true for the synchronized activity rhythm observed in pinealectomized birds of both species in LD, as well as for the damped rhythm that persists in pinealectomized house sparrows following an LD-to-DD transfer. The results are consistent with the hypothesis that the pineal and its periodic output of melatonin constitute only one component in a system of at least two coupled pacemakers. They also suggest that there are species differences in the relative role played by the pineal and other pacemakers in controlling circadian rhythms in behavior.     

Effects of shortened daylength and melatonin treatment on plasma prolactin and melatonin levels in pinealectomised and sham-operated ewes

Comparisons have been made between the effects of shortened daylength and melatonin treatment on plasma prolactin and melatonin levels in pinealectomised (Px) and sham-operated (Sh) ewes. Twenty-two anoestrous Merino crossbred ewes, maintained under normal grazing conditions, were assigned to four groups for a period of 9 weeks. Group 1 remained untreated (control), Group 2 was herded into a dark shed at 1600 h each day until dark (approx 4 h), ewes in Group 3 were injected with 100 μg melatonin s.c. at 1600 h each day and ewes in Group 4 were implanted with a melatonin capsule releasing 125–200 μg/day. Another group (Group 5) of 4 Px and 4 Sh ewes from the same flock was maintained in an animal house and subjected to shortened daylength (10. 5 h L : 13. 5 h D, lights off 1600 h). Three weeks after the treatments began, ewes in Groups 1–4 were exposed to a fertile ram and ewes in Group 5 to a vasectomised ram and the day of mating noted. No differences were evident between Groups 1–4 in the ewes' response to the ram, time taken to conceive, duration of gestation or number of lambs born. In untreated Px ewes no plasma melatonin (< 20 pg/ml) was found in either day or night samples, whereas intact animals showed the characteristic night-time rise. The silastic implants produced stable daytime blood levels of 90–120 pg/ml, whereas a single injection of 100 μg melatonin caused a transitory (2–3 h) rise. Shortened daylength (Group 2) or a single daily injection of melatonin (Group 3) lowered prolactin levels but only in ewes with an intact pineal gland, whereas melatonin implants (Group 4) caused a reduction in plasma prolactin in both Px and Sh sheep. The results indicate that light-induced alterations in prolactin production in sheep involve both the pineal gland and melatonin. Continuous melatonin release from implants caused changes in plasma prolactin levels similar to those seen following exposure to short days.     

Effect of maternal pinealectomy and reverse photoperiod on the circadian melatonin rhythm in the sheep and fetus during the last trimester of pregnancy

The present study tested the hypothesis that the nocturnal melatonin rhythm in the fetal sheep results from transfer across the placenta of melatonin from maternal circulation. Pregnant ewes were exposed to an artificial reverse photoperiod at about 100 days gestation (n = 6; lights on 10 h, 2200-0800 h PST). This treatment tested for entrainment in the ewe and its fetus of the 24-h pattern of melatonin production from the pineal gland. Other ewes were pinealectomized at 55 days post-breeding (n = 6), and similarly treated. Catheters were implanted and blood samples were collected between 117 and 142 days gestation at two 48-h periods, about every 0.5-4 h, to assess the pattern of melatonin in maternal and fetal circulations. In pineal-intact ewes and their fetuses, melatonin rhythms conformed to the reverse photoperiod, i.e. plasma melatonin concentrations were relatively low during the light period and significantly increased for the duration of darkness. In contrast, maternal pinealectomy abolished the melatonin rhythms in both the ewe and fetus; melatonin concentrations remained at or below the limits of detection. Pineal-intact sheep gave birth about 139 +/- 2 days (mean +/- SE, n = 4) at 1915 +/- 0.7 h and pinealectomized ewes (n = 5 of 6) lambed at 149 +/- 2 days at 0424 +/- 0.5 h. Finally, in lambs (n = 3) born to pinealectomized ewes, typical melatonin rhythms were present within the first week of life. The findings indicate that the maternal pineal gland is responsible for the 24-h pattern of melatonin in the ewe and its fetus during the last trimester of pregnancy.     

Changes in plasma tryptophan and melatonin content in penned sheep

The present study was undertaken to examine the relationship between the plasma levels of melatonin and its precursor tryptophan. No circadian changes in plasma total tryptophan content were evident which could be related to the marked night-time rise in plasma melatonin. An automated programmable blood sampling device suited to studies of circadian rhythms in blood constituents is described.     

Daily and circadian variation in the electroretinogram of the domestic fowl: effects of melatonin

Visual and circadian function are integrally related in birds, but the precise nature of their interaction is unknown. The present study determined whether visual sensitivity measured electroretinographically (ERG) in 7-week-old cockerels varies over the time of day, whether this rhythm persists in constant darkness (DD) and whether exogenous melatonin affects this ERG rhythmicity. ERG b-wave amplitude was rhythmic in LD and persisted in DD with peak amplitude during mid- to late afternoon in LD and mid-subjective day in DD, indicating that the ERG rhythm is endogenously generated. No daily or circadian variation in a-wave amplitude was observed, and ERG component latency and durations were not rhythmic. Intramuscular injection of 10 g/kg melatonin at ZT10 in LD significantly decreased b-wave amplitude but had no effect on a-wave. Intraocular injection of 600 pg melatonin, however, had no effect on any aspect of the ERG. These data indicate that a circadian clock regulates ocular sensitivity to light and that melatonin may mediate some or all of this effect. The level at which melatonin modulates retinal sensitivity is not known, but the present data suggest a central site rather than a direct effect of the hormone in the eye.Abbreviations DD constant darkness - ERG electroretinography - EW Edinger-Westphal nuclei - IMEL iodomelatonin - IO isthmooptic nucleus - LD light-dark cycle - SCG superior cervical ganglion - SCN suprachiasmatic nuclei - vSCN visual suprachiasmatic nucleus     

Seasonal variations in circadian rhythms of plasma melatonin in ruin lizards

We examined melatonin profiles of ruin lizards in different seasons (spring, summer, and autumn) under light:dark (LD) and concomitant responses when transferred to continuous darkness (DD) to determine the degree to which previously reported seasonally dependent effects of pinealectomy on locomotor behavior are related to melatonin secretion. The amplitude of the melatonin rhythm and the amount of melatonin produced over 24 h varied with season. In spring, the amount of melatonin produced was greatest and the amplitude 4- 5 times that found in summer or autumn. The degree of self-sustainment of the melatonin rhythm when transferred to DD also varied with season. In DD, melatonin levels remained high but did not exhibit circadian variation in spring. In summer, the melatonin profile persisted virtually unchanged in DD, showing the existence of a circadian rhythm. Finally, in the fall there was no circadian variation in DD and levels remained low. These responses correspond closely to previously reported effects of pinealectomy on locomotor behavior where there is little or no effect of pinealectomy in spring or fall but a profound alteration of locomotor behavior in summer. These results suggest that the seasonally dependent effects of pinealectomy on locomotor behavior in ruin lizards are related to a seasonally mediated change in the degree of self-sustainment of some component of the circadian pace-making system of which melatonin plays some role.     

Analysis of trough and peak of plasma melatonin circadian rhythm in ewes

This study evaluates the pattern of plasma melatonin during the trough and the peak of its daily rhythm. Blood samples from 8 ewes were collected every 3 h for a 48-h period. On the third day, blood samples were collected from 10:00 to 13:00 (trough) and from 20:00 to 23:00 (peak) every 20 min. Our results showed a robust daily rhythm of melatonin in both days of monitoring, with nocturnal acrophase. During the trough, a significant decrease was observed starting from the 10:40 with a progressive decrease about every 40 min. During the peak of the plasma melatonin daily rhythm, an increase was observed starting from the 20:40 with a progressive increase about every 40 min. These data could be taken in consideration to monitor the plasma melatonin variations during the 24 h, and for the administration of melatonin for breeding in ewes.     

Effect of age on circadian rhythm of prolactin in normal men

The 24 h secretion pattern of prolactin was studied in 9 young normal males (aged 22-46) and in 11 older normal men (aged 55-74). Despite considerably reduced duration and quality of sleep, the nocturnal surge in plasma prolactin in elderly men was the same as in young subjects. The overall 24 h secretion pattern and the absolute levels of prolactin are unaltered with age in normal men.     

Interactions between light and melatonin on the circadian clock of mice.

Melatonin and light synchronize the biological clock and are used to treat sleep/wake disturbances in humans. However, the two treatments affect circadian rhythms differently when they are combined than when they are administered individually. To elucidate the nature of the interaction between melatonin and light, the present study assessed the effect of melatonin on circadian timing and immediate-early gene expression in the suprachiasmatic nucleus (SCN) when administered in the presence of light. Male C3H/HeN mice, housed in constant dark in cages equipped with running wheels, were treated with either melatonin (90 microg, s.c.) or vehicle (3% ethanol-saline) 5 min prior to exposure to light (15 min, 300 lux) at various times in the circadian cycle. Combined treatment resulted in lower magnitude phase delays of circadian activity rhythms than those obtained with light alone during the early subjective night and advances in phase when melatonin and light were administered during the subjective day (p < .001). The reduction in phase delays with combined treatment at Circadian Time (CT) 14 was significant when light exposure measured 300 lux but not at lower light levels (p < .05). When light preceded melatonin administration, the inhibition of phase delays attained significance only when the light exposure reached 1000 lux (p < .05). Neither basal nor light-induced expression of c-fos mRNA in the SCN was modified by melatonin administration at CT 14 or CT 22. Together, these results suggest that combined administration of melatonin and light affect circadian timing in a manner not predicted by summing the two treatments given individually. Furthermore, the interaction is not likely to be due to inhibition of photic input to the clock by melatonin but might arise from a photically induced enhancement of melatonin's actions on circadian timing.     

Circadian and seasonal variation of the body temperature of sheep in a tropical environment

Nychthemeral and annual rhythms of the rectal temperature were determined for Corriedale sheep in a tropical climate. The minimum rectal temperature averaged 39.55° C at 0500 hours in summer, and 38.87° C at 0600 hours in winter. The maximum was 40.03° C in summer (1700 hours) and 39.33° C in winter (1830 hours). Annual cycle of the rectal temperature showed a minimum in July and maximum in December.     

Brood translocation and circadian variation of temperature preference in the ant Camponotus mus

Summary 1) When a thermal gradient (20–40° C) was established along a laboratory nest, Camponotus mus nurse workers showed a photoperiodic circadian rhythm of temperature preferences for brood rearing. Two different temperatures were daily selected to translocate the brood, i.e. 30.8° C selected at the middle of the photophase, and 27.5° C selected during the scotophase, 8 h later. 2) The daily temperature response of nurse workers consisted of paired high and low-temperature translocations, with a 8 hs-interval in between: high-temperature translocation was shown to be entrained by the photophase length, whereas low-temperature translocation was shown to be dependent on the precedent one. 3) Prey deprivation to the colony modified the brood transport behaviors resulting in translocations of only cocoons and large (ripe) larvae, stages in which the pupation processes are triggered. Small larvae and eggs remained located at 27.5° C. 4) Evaluation of pupa developmental time as well as percentage of pupa mortality at different temperature regimes allowed to construct an efficiency index relating pupa survival and cocoon developmental time. In the range of temperatures selected by nurses, the index reached its maximal values. 5) The ecological significance of these results is discussed.     

Effect of histamine and acetylcholine on hypophysial stalk plasma dopamine and peripheral plasma prolactin levels.

To further define the role of dopamine in the regulation of prolactin secretion, we studied the effect on prolactin and hypothalamic dopamine secretion of histamine and acetylcholine (ACh) injected into the lateral ventricle of urethane anesthetized diestrus-1 rats. Histamine (10 μg) caused a 592% increase in plasma prolactin levels and a 26% decrease in stalk plasma dopamine levels. ACh (50 μg) caused a 2090% increase in plasma prolactin levels but no significant change in stalk plasma dopamine concentration.To determine if the 26% fall in stalk plasma dopamine following histamine administration could account for the 6-fold increase in plasma prolactin, we measured the effect on prolactin secretion of a similar decrease in administered dopamine. During an infusion of physiologic levels of dopamine, a 25% decrease in arterial plasma dopamine concentration resulted in only a 2-fold increase in prolactin secretion.The results of these experiments suggest that the effect of histamine on prolactin secretion may be mediated in part by decreased hypothalamic secretion of dopamine but that an additional hypothalamic hormone is probably involved. The stimulatory effect of ACh on prolactin secretion is not mediated by dopamine. These data are consistent with the growing evidence for the participation of multiple hypothalamic factors in the regulation of prolactin secretion.     

The circadian body temperature rhythm in the elderly: effect of single daily melatonin dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age-dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age-dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra- and inter-individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38+/-0.19 degrees C vs. 36.17+/-0.21 degrees C) and circadian amplitude (0.33+/-0.01 degrees C vs. 0.26+/-0.01 degrees C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19+/-1.66 vs. 16.93+/-3.08 h). However, the inter-individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter-daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1 degrees C and the amplitude increased to 0.34+/-0.01 degrees C, a similar value to that found in young adults. This was probably due to the increase of the inter-daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter-individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age-dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep-improving effects.