Although there is a circadian rhythm in blood melatonin concentrations in humans, the problems associated with frequent blood collection limit the use of this rhythm in the investigation of the circadian system and in the diagnosis and treatment of chronobiological disorders. Therefore, to establish a convenient, non-invasive technique for monitoring melatonin circadian rhythmicity, we compared the melatonin concentrations in blood samples collected from five subjects every 2-4 h over a 26 h period, with the melatonin concentrations in saliva samples and with the total amount of 6-hydroxymelatonin sulphate excreted in the urine during 2-h periods. There was significant correlation between serum and salivary melatonin concentrations (r = 0.81, P less than 0.001), and between serum melatonin concentrations and 6-hydroxymelatonin sulphate excretion rates (r = 0.72, P less than 0.001). The results demonstrate that both salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates are reliable indices of serum melatonin concentrations. These measurements, in combination with frequent sample collection, provide two convenient, non-invasive techniques for monitoring melatonin circadian rhythmicity.
We have investigated the effect of pinealectomy of ewes in pregnancy on the presence of the diurnal rhythm in fetal and maternal plasma concentrations of melatonin. Six ewes were pinealectomized between 104 and 118 days of gestation. Fetal and maternal blood samples were collected during 24-h periods between 125 and 140 days of gestation in the pinealectomized ewes and in an intact control (n = 4). There was a significant diurnal rhythm in both fetal and maternal plasma concentrations of melatonin in the control group. In this group, the fetal and maternal plasma melatonin concentrations were significantly higher in the dark (128.4 +/- 6.2 and 192.2 +/- 10.7 pmol/l respectively) than in the light (46.2 +/- 4.2 and 25.8 +/- 2.1 pmol/l respectively). However there was no diurnal rhythm in either the fetal or maternal plasma melatonin concentrations in the pinealectomized group between 125 and 140 days of gestation. In contrast to the control animals, there was also no light-dark difference in the fetal or maternal plasma melatonin concentrations in four pinealectomized animals sampled frequently in the 3-7 days preceding delivery (mean length of gestation 146.5 days). However, in the pinealectomized sheep there was a gradual increase in the combined light-dark fetal plasma melatonin concentrations during late gestation from 27.9 +/- 2.8 pmol/l (at 15-20 days before delivery) to 95.2 +/- 14.1 pmol/l on the day of delivery. We have therefore demonstrated that the maternal pineal is the major source of the diurnal rhythm in maternal and fetal plasma melatonin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Melatonin was administered intravaginally in Silastic tubing to adult and prepubertal ewes. In Exp. 1, ewe lambs (born early March) were given intravaginal melatonin implants at a mean age (+/- s.e.m.) of 7.5 +/- 0.1 weeks (Group E, N = 10) or 19.4 +/- 0.2 weeks (Group L, N = 10). The third group (Group C, N = 10) received empty implants. In Exp. 2 mature ewes were given implants on 13 May (Group E, N = 10) or 18 July (Group L, N = 10) or received empty implants (Group C, N = 10) on one of these two dates. Blood samples were taken twice weekly for progesterone assay. In Exp. 1 the mean age (+/- s.e.m.) at puberty (progesterone greater than 2 nmol/l for two consecutive samples) was 35.4 +/- 0.8 weeks. Puberty was advanced by 5.2 weeks in Group L lambs, occurring at a mean age of 30.2 +/- 0.7 weeks (P less than 0.001). In Group E lambs the timing of puberty was unaltered, occurring at a mean age of 34.8 +/- 0.6 weeks. Mature ewes in Group L (Exp. 2) showed increased incidence of ovarian activity (9/10 ewes cycling by 26 September) compared with the control ewes (1/10) (P less than 0.001), but there was no effect in Group E ewes (3/10). The results demonstrate that continuous melatonin administration to adult and prepubertal ewes can mimic the effect of short days in terms of the reproductive response, and that the present and previous exposure to melatonin is critical in determining the response.
ABSTRACT. We have compared the roles of neurologic maturity and environmental time cues in the development of the entrained circadian sleep-wake rhythm in the preterm and term human infant. The preterm infants (n = 19) spent some time after birth in a hospital nursery with no environmental time cues, whereas the term infants (n = 22) were exposed from birth to a cyclical light and dark environment with one major caregiver. The circadian sleepwake rhythm in the preterm infants entrained after a similar time of exposure to an environment with daily time cues but at an earlier postconceptional age when compared with the term group. We conclude, therefore, that it is the length of exposure to environmental time cues, rather than neurologic maturity, that determines the entrainment of the circadian rhythm of sleep and wakefulness in the human infant. (Pediarr Res 29: 381-384, 1991) The daily sleep-wake cycle in the adult is a circadian rhythm, i.e. it is a behavioral rhythm that is generated by an endogenous biologic clock and in the absence of external time cues it "freeruns" with a periodicity of approximately 25 h (1). Normally, however, the circadian sleep-wake pattern is entrained or synchronized to an exact 24-h period by external time cues that are known as zeitgebers. It has been proposed that the light-dark cycle and also social cues act as zeitgebers on the endogenous circadian pacemaker to synchronize the human sleep-wake cycle to a 24-h period ( 1 ).Although there is extensive literature that documents that sleep is consolidated toward the night by the 6th to 14th wk of life (2-6), there have been few attempts to define the factors that determine the timing of entrainment of the infant's circadian sleep-wake rhythm to the day-night cycle. It has been widely accepted that the emergence of an entrained circadian sleepwake pattern in the human infant is predominantly the result of maturation of the CNS (2-6). This is supported by the demonstration using spectral analysis that sleep-wake activity has a more prominent 24-h component in term infants when compared with preterm infants at the same postnatal age (7-13 wk),-.It may be misleading, however, to compare the development of circadian sleep-wake rhythms in pre-and full-term infants without taking into account the differences in the range of zeitgebers that these infants are exposed to after birth. A fullterm infant born at home or in hospital, where "rooming-in" with the mother is the normal practice, is exposed to a cyclical light-dark environment and the circadian behavioral and social patterns of a single caregiver. In contrast, the preterm infant will spend some time after birth in a hospital neonatal nursery where there is constant illumination and where there are several different caregivers in any 24-h period (8). Any difference between term and preterm infants in the timing of the development of an entrained circadian sleep-wake pattern may therefore not only be due to differences in maturity but also to exposure to a different range of zeitgeb...
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