摘要:

Abstract:A role for melatonin in humans is becoming evident in an increasing number of clinical situations. Marked variations in the magnitude of the nocturnal melatonin peak are observed throughout the human lifespan. The highest levels occur in children and then fall during puberty and further during adulthood. A negative correlation between circulating melatonin and sex steroids has been observed in a number of instances, and appears to be independent of concomitant gonadotrophins. No clear melatonin pattern has been observed in pituitary tumors, but in large lesions that involve the hypothalamus, a reduced nocturnal rise has been reported. Reported effects of exogenously administered melatonin are variable, probably reflecting differences in dose and timing; a slight stimulation of prolactin, as well as a partial inhibition of gonadotrophins, has been reported, which explains its utility as an oral contraceptive, associated with a progestogen. A potential clinical use of melatonin as an oncostatic drug still awaits confirmation, although experimental data firmly support this possibility. The indole has also been used to hasten entrainment of subjects travelling across various time zones, and has been found to be specially useful in eastward travel. Finally, changes in the normal melatonin circadian pattern have been reported in psychiatric diseases and in sudden infant death syndrome.

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00231.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Early investigations of the effect of sleep deprivation on plasma melatonin reported no major changes. Recently, 36 hrs of sleep deprivation was reported to elevate melatonin levels on the post‐sleep deprivation night. Given these contradictions melatonin, Cortisol, prolactin, and thyroid stimulating hormone before, during, and, after sleep deprivation were examined in nine healthy young males following one night of sleep deprivation. Hormone levels at hourly intervals, for each night, were statistically analyzed by a repeated measures, two‐way factorial ANOVA. ANOVA was also performed for measures of area under the curve (AUC). No significant differences were observed for melatonin levels. Cortisol was significantly higher on the sleep deprivation night presumably reflecting the aroused state accompanying being awake; however, there were several time points on the control night when it was elevated also. Prolactin was higher on the post‐sleep deprivation and control nights but did not rise on the deprivation night, indicating a useful nonpolysomnographic index for discriminating overnight sleep and awake states. TSH levels showed a similar rise during the control and sleep deprivation nights, but remained flat on the post‐sleep deprivation night. It appears that the pineal is insulated against feedback from changes to the level of arousal accompanying sleep and wakefulness. In comparison, Cortisol, prolactin, and TSH levels vary with these states and are, therefore, useful indices of arousal and sle

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00232.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The secretion of melatonin by the pineal has been promoted as a direct monitor of adrenergic function in depressive illness. However, discrepant findings have been reported, possibly reflecting a complex adrenergic regulation of pineal output. In order to clarify the anatomical localization and relative density of β‐adrenergic receptors and their subtypes in human pineal, quantitative autoradiographic analysis was conducted of β‐adrenergic receptors in postmortem specimens using the high affinity radioligand125I‐pindolol. Dense specific binding was found throughout the gland. β1,‐adrenergic receptors were more numerous, but β2‐receptors were present in an overlapping anatomical distribution with

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00233.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Melatonin research has primarily utilized blood as the source of samples, but there is now increasing interest in measuring levels of the hormone found in saliva. One impediment to this approach is that several melatonin assays involve a column‐extraction step that can prove very time‐consuming or even impossible when salivary samples are excessively viscous. We have treated 67 samples with dithiothreitol to enhance their passage through the column. Following this treatment, all samples passed freely through the columns. The minimum and maximum values measured were 0.7–50.0 pg/ml for the untreated controls and 1.0–51.9 pg/ml for the treated samples. The means (± SEM) for these groups were 9.5 ± 1.6 and 9.9 ± 1.7, respectively, and were not significantly different from one another as assessed by Student's t‐test (P = 0.08). In summary, we have found that this technique permits us to obtain values on samples which would otherwise be unusable and that such treatment does not alter the melatonin values yielded by

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00234.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The circadian rhythm of melatonin production was studied using on‐line, in vivo microdialysis in the rat pineal gland. With this technique it was possible to record a pronounced melatonin rhythm with very high time resolution. Three phase‐markers of the rhythm were calculated from the data, indicating increase (IT50), decrease (DT50) and amplitude of the rhythm. Comparing these phase markers led to several conclusions. Entrainment of the rhythm under constant darkness was performed with melatonin administration at different circadian stages [circadian time (CT) 8 and CT12] and for different periods of time (2 weeks and 4 weeks). Also, entrainment was established by applying 15 min light pulses at CTO. Entrainment of IT50with melatonin partially uncoupled it from DT50. Four weeks entrainment in constant darkness (DD) caused a phase‐delay in DT50of 2.2 hr. Entrainment of IT50with light at CTO for 2 weeks in DD caused a phase‐advance in DT50of 1.3 hr. The entrainment with melatonin was restricted to a narrow window for melatonin to be applied, since injections at CT8 did not result in entrainment. Exogenous melatonin reduced the amplitude of the rhythm of endogenous melatonin. This effect was not circadian time dependent, since administration at CT8 for 2 weeks and at CT12 for 4 weeks resulted in a highly significant decrease. Light did not seem to have an effect on the amplitude. The data presented here provide us with new information about the nature of entrainment by melatonin. Since the present development of melatonergic agents for clinical use focuses on the entrainment capacity, effects of these compounds on amplitude of circadian rhythms needs to be addressed. In vivo microdialysis seems to be a good technique f

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00235.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Melatonin binding sites were characterized in rat spleen crude membranes. The specific binding of 2‐[125I]iodomelatonin by spleen crude membranes fulfills all the criteria for binding to a receptor site. Thus, binding was dependent on time and temperature, stable, specific, and increased under constant light exposure and after pinealectomy. In competition studies, the specific binding of 2‐[125I]iodomelatonin to spleen crude membranes was inhibited by increasing concentrations of native melatonin. Scatchard analysis showed that the data were compatible with the existence of two classes of binding sites: a high affinity site with a Kdof 0.53 nM and a binding capacity of 2.52 pM, and a low‐affinity site with a Kdof 374 nM and binding capacity of 820 pM. Moreover, binding of 2‐[l25I]iodomelatonin exhibited day‐night variations with the highest binding observed late during the light period, and the lowest binding was observed late at night. However, binding of 2‐[125I]iodomelatonin to membranes remained high when animals were kept under light exposure at night. Results support the hypothesis of a regulatory role of melatonin on the immune system in which melatonin downregulates its own b

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00236.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Fractures of deep‐frozen and freeze‐dried pineal glands were analysed for elemental composition by means of X‐ray microanalysis with a scanning electron microscope. The results from young adults (3 months old) were compared with those from aged animals (24 months old); significant increases in S, Ca, Al, Si, and Fe were observed in aged animals when compared to young adults. There were no significant differences with Na, Mg, CI, K, Ti, Cr, Mn, Ni, Cu, Zn, whereas a decrease of P was observed in aged animals when compared to young adults. Whether the changes observed in elemental composition have a direct effect on the activity and production of metalloenzymes and the overall physiology of the pineal gland are disc

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00237.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Because of the overexpression of the enzyme superoxide dismutase, individuals with Down syndrome (DS) are believed to suffer from increased oxidative stress as a result of the excessive production of oxygen‐based free radicals; their exposure to higher than normal free radical production may account in part for signs of premature aging, early onset of cataracts, and of Alzheimer's disease. Free radicals are normally neutralized by free radical scavengers and other antioxidants. The pineal hormone melatonin is a potent scavenger of both the hydroxyl and peroxyl radicals, both of which are highly toxic, and a stimulator of the antioxidative enzyme glutathione peroxidase. Considering this, we deemed it important to define the day/night rhythm and levels of melatonin production in DS subjects. To do this, we assessed the urinary excretion of the chief melatonin metabolite, 6‐hydroxymelatonin sulfate, throughout a 24 hr period in DS subjects; comparisons were made with the metabolite levels in the urine of non‐Down siblings and parents of the DS subjects. All 8 non‐Down subjects exhibited what was classified as normal urinary excretion of 6‐hydroxymelatonin sulfate with the usual low daytime and high night‐time levels of the melatonin metabolite. Of 12 DS subjects studied, 10 exhibited the normal day/night rhythm in urinary 6‐hydroxymelatonin sulfate levels; 2 subjects were devoid of a rhythm. However, when all the data from each group were averaged, there were no noticeable differences in the absolute levels or 24 hr variations in urinary 6‐hydroxymelatonin sulfate excretion between DS and no

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00238.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY