Nocturnal Serum Melatonin Levels Research Articles

Meta-analysis of melatonin levels in cluster headache-Review of clinical implications.

Cluster headache (CH) has been associated with circadian disturbances. The present systematic review examined available evidence for the utilization of melatonin (MT) in CH prophylaxis. First, case-control studies assessing nocturnal MT or its urine-expelled metabolite 6-sulfatoxymelatonin (aMT6s) in CH individuals and healthy controls (HC) were reviewed and meta-analyzed. Secondly, the results from randomized controlled trials (RCTs) and non-randomized studies evaluating MT's use in the prevention of CH were discussed. Literature search included MEDLINE, EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey. Bouts and remissions were assessed separately. Ten case-control studies (adult participants) were retrieved. Seven evaluated serum MT; meta-analysis involved only three of them (due to deficient reporting, n: bout=31, remission=38, HC=31). Results were compatible with lower nocturnal serum MT levels during bouts [bout-HC; FE-MD=-29.89pg/mL, 95% CI=(-46.00, -13.78), remission-HC; FE-MD=-2.40pg/mL, 95% CI=(-16.57, 21.38), bout-remission; RE-MD=-32.10pg/mL, 95% CI=(-56.78, -7.42)]. Nocturnal urinary melatonin was appraised in two studies, but reporting issues impeded the capitalization of the results. Nocturnal urine aMT6s was evaluated by two studies (n: bout=29, remission=22, HC=20), and pooled results were indicative of lower aMT6s concentration in CH individuals during both active and inactive periods [bout-HC; FE-MD=-9.63μg/nocturnal urine collection, 95% CI=(-14.40, -4.85), remission-HC; FE-MD=-9.12μg/nocturnal urine collection, 95% CI=(-14.63,-3.62), bout-remission; FE-MD=-0.58μg/nocturnal urine collection, 95% CI=(-4.58, 3.42)]. Regarding CH prophylaxis, one RCT and two non-randomized trials were retrieved, involving a total of 41 adult CH individuals (11-episodic, 31-chronic) and rendering the deduction of any conclusions precarious. Overall, available data for the role use of MT in CH are insufficient and inconclusive. Complementary studies evaluating endogenous MT concentrations and MT administration to patients with CH are warranted.

Nocturnal serum melatonin levels in sulfur mustard exposed patients with sleep disorders

BackgroundSulfur mustard (SM) exposure causes respiratory disorders, progressive deterioration in lung function and mortality in injured victims and poor sleep quality is one of the most common problems among SM-exposed...

Diurnal and nocturnal serum melatonin concentrations after treatment with continuous positive airway pressure in patients with obstructive sleep apnea.

INTRODUCTION Melatonin secretion, one of the main factors controlling the sleep-wake rhythm, may be disrupted in patients with sleep disorders. OBJECTIVES The aim of the study was to evaluate the profile of circadian melatonin secretion in patients with obstructive sleep apnea (OSA) and to assess the impact of 2-day and 3-month treatment with continuous airway pressure (CPAP) on diurnal and nocturnal serum melatonin levels. PATIENTS AND METHODS Serum melatonin levels were evaluated in 71 untreated patients with OSA and 18 healthy controls at 6 time points: 10 AM, 2 PM, 6 PM, 10 PM, 2 AM, and 6 AM. The measurements were repeated after 2 days and 3 months of CPAP treatment. RESULTS Melatonin secretion rhythm was altered in 25.4% of the patients with OSA. In patients with preserved secretion rhythm, the serum melatonin level was significantly lower at 2 AM and 6 AM, compared with healthy controls: 68.2 pg/ml (interquartile range [IQR], 30.1-109.8 pg/ml) vs 109.1 pg/ml (IQR, 63-167.9 pg/ml), P = 0.02 and 40.8 pg/ml (IQR, 20.8-73.2 pg/ml) vs 67.7 pg/ml (IQR, 32.7-131.7 pg/ml), P = 0.04, respectively. Melatonin levels did not change significantly after the 2-day and 3-month CPAP treatment. However, at 3 months, a shift of the peak melatonin concentration to 2 AM was observed in patients with an altered secretion rhythm. CONCLUSIONS OSA has a significant effect on serum melatonin levels. Neither short-term nor long-term CPAP treatment significantly changes melatonin concentrations; however, our results seem to indicate that a 3-month CPAP treatment may be helpful in restoring the physiological rhythm of melatonin secretion in patients with OSA.

The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. AANAT, which is expressed in the pineal gland, retina, and various other tissues, catalyzes the conversion of serotonin to N-acetylserotonin and is the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AANAT can be used to treat patients with circadian rhythm disorders that are associated with specific circadian rhythm alterations, such as shift work disorder. In the present study, we screened modulators of AANAT activity from the water extracts of medicinal plants. Among the 267 tested medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition of AANAT activity. Myricetin (5,7,3′,4′,5′-pentahydroxyflavonol), a main component of the Myricae Cortex, strongly inhibited the activity of AANAT and probably block the access to the substrate by docking to the catalytic residues that are important for AANAT activity. Myricetin significantly decreased the nocturnal serum melatonin levels in rats. In addition, the locomotor activity of rats treated with myricetin decreased during the nighttime and slightly increased throughout the day. These results suggest that myricetin could be used as a therapy to increase nighttime alertness by changing the circadian rhythm of serum melatonin and locomotor activity.

Melatonin secretion and metabolism in patients with hepatic encephalopathy

The rhythm of melatonin secretion and its blood level changes in cirrhotic patients, but the causes of these alterations have not been sufficiently appreciated. The aim of study was to estimate the dependence between melatonin secretion and metabolism and the severity of hepatic encephalopathy. The study included 75 alcoholic cirrhotic patients (A, B, C) with hepatic insufficiency and 25 healthy subjects (group K). Three groups of patients were identified, 25 patients each, with grade 1, 2, and 3 hepatic encephalopathy according to West-Haven Scale. Immunoenzymatic method was used to measure serum melatonin (at 02:00 h and 09:00 h) level and 6-sulfatoxymelatonin (6-HMS) excretion in the urine (during night and day). Nocturnal serum melatonin levels (pg/mL) in groups were: K-57.1 ± 11.4, A-38.5 ± 11.2, B-53.4 ± 17.9, C-79.5 ± 27.9 (P < 0.01); whereas diurnal levels were: K-10.9 ± 3.5, A-33.5 ± 12.0, B-53.8 ± 23.1, C-98.5 ± 34.6 (P < 0.01). Similar differences were found in the evaluation of 6-HMS excretion (μg/9 h) in urine at night: group K-23.4 ± 14.4, A-16.6 ± 5.4, B-14.3 ± 6.2 (P < 0.01), C-3.3 ± 1.5 (P < 0.001). Diurnal 6-HMS excretion (μg/15 h) was lower only in group C and it was respectively: K-6.9 ± 3.4, A-7.1 ± 1.7, B-7.6 ± 1.7, C-4.3 ± 2.2 (P < 0.001). Serum ammonia concentrations (μg/dL) were: group K-30.4 ± 8.9, A-51.8 ± 25.4 (P < 0.05), B-73.0 ± 29.8 (P < 0.001), C-107.5 ± 34.8 (P < 0.001). No correlation between melatonin and ammonia levels in all groups was found. The elevated melatonin blood levels both at night and day may account for some of the clinical manifestations of hepatic encephalopathy (daytime sleepiness, fatigue).

Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study.

The pineal gland is an adaptive organ that precisely regulates the biological rhythms of melatonin brain hemostasis. Variation in the regulation of melatonin rhythms is a likely cause of depressive disorder. The purpose of this study was to measure serum melatonin levels in patients with major depressive disorder (MDD) and normal control subjects. Analytical cross-sectional study at the industrial medical unit of the Iron Smelting Company of Isfahan, Iran. The morning and nocturnal serum melatonin levels of patients and controls were measured using the enzyme-linked immunosorbent assay (ELISA) method. All data were assessed using variance analysis. The morning and nocturnal serum melatonin levels of depressed and healthy subjects differed (P < 0.05). The nocturnal serum melatonin levels of depressed women were lower than those of depressed men (P < 0.05). The findings of this study showed that the nocturnal serum melatonin levels in the depressed patients were lower than in the controls. Thus, the peak melatonin phase in the depressed patients was reached with delay.

Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume. Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration. Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed. Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

The association of nocturnal serum melatonin levels with major depression in patients with acute multiple sclerosis

The association of nocturnal serum melatonin levels was investigated in acute multiple sclerosis (MS) patients with major depression (MD). The sample comprised 13 patients with MD and 12 with no psychiatric disorders admitted to our clinic due to acute MS attacks. Psychiatric evaluation was performed with the Structured Clinical Interview for DSM-IV (SCD-I). The level of depressive symptoms was assessed with the Beck Depression Scale (BDS). Blood samples were taken from the patients to determine melatonin level at 03.30h and 10.00h before steroid treatment started. Melatonin levels were determined using the ELISA test. Nocturnal serum melatonin levels (21.2 ± 17.1 pg/ml) of the patients with MD were significantly lower than those (51.5 ± 18.3 pg/ml) of the patients without MD. A significant negative correlation was found between BDS scores and nocturnal serum melatonin levels. These findings suggest that a melatonin deficiency may be among the factors involved in the occurence of depression in MS patients.

No effects of 900 MHz and 1800 MHz electromagnetic field emitted from cellular phone on nocturnal serum melatonin levels in rats

In this study, the effects of exposure to a 900 MHz and 1800 MHz electromagnetic field (EMF) on serum nocturnal melatonin levels of adult male Sprague-Dawley rats were studied. Thirty rats were used in three independent groups, 10 of which were exposed to 900 MHz, 10 of which were exposed to 1800 MHz and 10 of which were sham-exposed (control). The exposures were performed 30 min/day, for five days/week for four weeks to 900 MHz or 1800 MHz EMF Control animals were kept under the same environmental conditions as the study groups except with no EMF exposure. The concentration of nocturnal melatonin in the rat serum was measured by using a radioimmunoassay method. There were no statistically significant differences in serum melatonin concentrations between the 900 MHz EMF group and the sham-exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5 pg/mL in the sham-exposed group and 34.97 +/- 5.1 pg/mL in the 900 MHz EMF-exposed group. Also, there were no statistically significant differences in serum melatonin concentrations between the sham-exposed group and the 1800 MHz EMF-exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5 pg/mL in the sham-exposed group and 37.96 +/- 7.4 pg/mL in the exposed group. These results indicate that mobile phones, emitting 900 and 1800 MHz EMF, have no effect on nocturnal serum melatonin levels in rats.

Elevated levels of oxidized low-density lipoprotein and impaired nocturnal synthesis of melatonin in patients with myocardial infarction

This study was designed to investigate the relationship between nocturnal serum melatonin (MEL) levels and oxidized low-density lipoprotein (OxLDL) in patients with acute coronary syndrome (ACS). OxLDL plays a pivotal role in the development of atherosclerosis. Patients with coronary heart disease have an impaired nocturnal secretion of MEL. To date, there are no clinical human studies concerning the relationship of MEL to low-density lipoprotein (LDL) oxidation in patients with acute myocardial infarction (AMI). The study population contained 60 patients with AMI and 60 control subjects. Levels of circulating OxLDL were measured by a monoclonal antibody 4E6-based competition ELISA. Levels of circulating MEL were measured by an enzyme-immunoassay kit after chloroform extraction. Comparison of levels between AMI and controls, adjusted for age, revealed significantly higher nocturnal serum OxLDL levels (95.47 ± 6.81 versus 68.35 ± 4.07 U/l; p = 0.004) in the AMI subjects. Nocturnal serum levels of MEL were lower in AMI than the control group (20.97 ± 3.90 versus 53.19 ± 7.80 pg/ml; p = 0.009). Serum levels of total, high-density lipoprotein (HDL), and LDL cholesterol did not differ between the groups. Multiple regression analysis was performed on cases to study the association between AMI and serum levels of OxLDL and MEL (OR: 2.93; 95% CI, 2.89–2.98, p = 0.01 and OR: 0.94; 95% CI, 0.89–0.97, p = 0.02, respectively). This study demonstrates for the first time an independent association between nocturnal levels of OxLDL and MEL in patients with AMI. Additional population studies are necessary to further document these.

Does hepatic metabolism of melatonin affect the endogenous serum melatonin level in man?

Melatonin (MT) is metabolized in the liver by cytochrome P450 (CYP) 1A2 but its importance for the metabolic process has not been fully elucidated. Therefore, the objective of this investigation was to study whether patients with different CYP1A2 activity would have different nocturnal serum MT levels. For that purpose serum MT concentrations were determined every second hour during the night in 12 healthy subjects and their MT areas under the curve (MT-AUCs) were calculated. Caffeine (CA) clearance was determined in advance. It is generally accepted that CA clearance reflects CYP1A2 activity. This made it possible to evaluate whether a relationship prevails between endogenous MT-AUCs and CYP1A2 activity. If CYP1A2 is of importance for the metabolism of MT one would expect to find an inverse correlation between the MT-AUCs and the CA clearance. However, such correlation did not exist in the current study (Rs=-0.021, NS). Since endogenous MT-AUC is dependent not only on MT elimination by CYP1A2 but also on MT secretion, it is possible that an increased MT secretion counter-balances an increased hepatic MT metabolism. If so, this could explain why the MT-AUCs and the CA clearance values were not inversely correlated in this study.

Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes.

The present study was carried out to identify the cytochrome P450 enzyme(s) involved in the 6-hydroxylation and O-demethylation of melatonin. The formation kinetics of 6-hydroxymelatonin and N-acetylserotonin were determined using human liver microsomes and cDNA yeast-expressed human enzymes (CYP1A2, 2C9 and 2C19) over the substrate concentration range 1-1000 microM. Selective inhibitors and substrates of various cytochrome P450 enzymes were also employed. Fluvoxamine was a potent inhibitor of 6-hydroxymelatonin formation, giving 50 +/- 5% and 69 +/- 9% inhibition at concentrations of 1 microM and 10 microM, respectively, after incubation with 50 microM melatonin. Furafylline, sulphaphenazole and omeprazole used at low and high concentrations substantially inhibited both metabolic pathways. cDNA yeast-expressed CYP1A2, CYP2C9 and CYP2C19 catalysed the formation of the two metabolites, confirming the data obtained with specific inhibitors and substrates. Our results strongly suggest that 6-hydroxylation, the main metabolic pathway of melatonin, is mediated mainly, but not exclusively, by CYP1A2, the high-affinity enzyme involved in melatonin metabolism, confirming the observation that a single oral dose of fluvoxamine increases nocturnal serum melatonin levels in healthy subjects. Furthermore, the results indicate that there is a potential for interaction with drugs metabolised by CYP1A2 both at physiological levels and after oral administration of melatonin, while CYP2C19 and CYP2C9 are assumed to be less important.

Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease.

A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin concentration) in patients with chronic stable or unstable coronary disease and in a group of age-matched controls. Three groups of individuals were studied: a) 24 healthy subjects (mean age: 63 +/- 13 yr); b) 32 patients with chronic, stable, coronary disease (62 +/- 11 yr); and c) 27 patients with unstable angina (62 +/- 12 yr). For 6-sulphatoxymelatonin measurement, urine was collected from 18:00 to 06:00 hr, within 48 hr of hospitalization in the case of unstable angina. 6-Sulphatoxymelatonin was measured by a specific radioimmunoassay. Urinary 6-sulphatoxymelatonin excretion was significantly lower in unstable angina patients than in healthy subjects or in patients with stable angina. 6-Sulphatoxymelatonin correlated negatively with age in healthy subjects, but not in coronary patients. 6-Sulphatoxymelatonin excretion in patients treated with beta-adrenoceptor blockers did not differ significantly from coronary patients not receiving beta-blockers. The results indicate that patients with coronary disease have a low melatonin production rate, with greater decreases in those with higher risk of cardiac infarction and/or death.

Nocturnal serum melatonin profile in major depression in children and adolescents.

In major depression, biological rhythm disturbances in sleep, appetite, and mood suggest dysregulation in neuroendocrine functions, possibly in the pineal gland. In this study, pineal gland function was examined by measuring nocturnal serum melatonin levels during both wakefulness and sleep in depressed children and adolescents. Twenty-two youths aged 8 to 17 years primarily with major depression were compared with 19 controls. Blood samples were drawn every half hour from 6 PM to 7 AM. Nocturnal serum melatonin levels were measured by radioimmunoassay. The overall nocturnal serum melatonin profile from 6 PM to 7 AM was significantly higher (mean +/- SD, 0.18 +/- 0.14 nmol/L) in the depressed group than in the controls [mean +/- SD, 0.15 +/- 0.10 nmol/L, F(1,26) = 4.37, P < .05]. In dim light, when the subjects were awake, no difference existed between the 2 groups. After lights-out, from 10 PM to 7 AM, the melatonin profile rose in both groups; however, the depressed group had a significantly higher increase (mean +/- SD, 0.24 +/- 0.14 nmol/L) than the controls [mean +/- SD, 0.18 +/- 0.07 nmol/L, F(1,26) = 4.93, mean square error = 0.11, P = .04]. Post hoc analysis showed a significantly higher melatonin profile in depressed subjects without psychosis (n = 15) than in depressed subjects with psychosis (n = 7) or in the controls. Measuring the overall nocturnal serum melatonin profile during darkness may help to differentiate children and adolescents with major depression without psychosis from those with psychosis and from controls.

Testosterone treatment alters melatonin concentrations in male patients with gonadotropin-releasing hormone deficiency.

Recently, we demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. As testosterone (T) can be aromatized to estradiol (E2), and both T and E2 increase during T enanthate treatment, we were interested in determining whether T treatment (when T and E2 levels were well matched with pubertal control values) has an effect on melatonin levels in these patients. We measured nocturnal serum melatonin levels during the administration of 250 mg testosterone enantale/month for 4 months in 12 male patients with idiopathic hypogonadotropic hypogonadism (IGD; n = 6) and delayed puberty (DP; n = 6). Serum samples for melatonin and LH determinations were obtained every 15 min from 1900-0700 h in a controlled light-dark environment. The results of melatonin profiles were compared with the pretreatment values in each group and with values obtained in six normal pubertal male controls. After 4 months of testosterone treatment, all patients attained normal serum testosterone (19.5 +/- 3.7 in IGD vs. 20.8 +/- 4.1 nmol/L in DP) and E2 levels (83 +/- 12 in IGD vs. 84 +/- 9 pmol/L in DP). Serum LH levels were suppressed in all patients during T treatment (0.12 +/- 0.1 in IGD vs. 0.12 +/- 0.2 IU/L in DP). Before T treatment, patient melatonin levels were greater than those in age-matched pubertal controls. Melatonin levels were equal in patients and controls when T and E2 levels were well matched. Mean (+/- SD) dark-time melatonin levels decreased from 286 +/- 23 to 157 +/- 36 pmol/L in IGD and from 217 +/- 32 to 133 +/- 47 pmol/L in DP (vs. 183 +/- 64 pmol/L in controls). The integrated melatonin values decreased to normal (from 184 +/- 16 to 102 +/- 21 in IGD and from 142 +/- 19 to 90 +/- 26 pmol/min.L x 10(3) in DP vs. 119 +/- 61 pmol/min.L x 10(3) in controls). The intraindividual variations in melatonin levels ranged from 7.2-14.5%. These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion. T treatment decreased melatonin secretion to normal levels. The results suggest that in GnRH-deficient male patients, sex steroids, rather than LH, modulate pineal melatonin in a reverse fashion.

Decreased Serum Melatonin Levels in Rats with Experimental Autoimmune Uveitis/Pinealitis and in Patients with Uveitis

The authors measured serum levels of the pineal hormone melatonin to investigate the possibility of pineal dysfunction in both rats with experimental autoimmune uveitis/pinealitis (EAU/EAP) and uveitis patients. The serum melatonin concentrations of EAU/EAP rats were measured by radioimmunoassay over a 24-hour (h) period, and in uveitis patients at night (0200 h). Melatonin concentrations were assayed in six patients with Behçet's disease, four with Vogt-Koyanagi-Harada (VKH) disease, three with sarcoidosis, three with Kirisawa-type uveitis, and one with tubulointerstitial nephritis and uveitis syndrome. Nocturnal serum melatonin levels were significantly lower in Lewis rats with EAU/EAP (2200 h: 33.6±20.4 pg/ml, 0200 h: 43.2±13.9 pg/ml) than in the controls (2200 h: 117.5±25.3 pg/ml, 0200 h: 132.4±20.2 pg/ml) (p>0.01, at 2200 h and 0200 h). Melatonin levels were significantly lower in VKH disease (20.7±10.5 pg/ml) (p>0.01) and Behçet's disease (42.1±42.5 pg/ml) (p>0.05) than in the controls (79.4±36.7 pg/ml). These results suggest that there is a decrease in pineal gland function due to pinealitis in EAU/EAP rats. The markedly decreased nocturnal serum melatonin levels may also be related to the presence of retinal uveitogenic antigens in uveitis patients.

Major affective disorders: Prospective clinical course during a 5- to 7-year follow-up in relation to neuroendocrine function tests

This study reports on the relationships between neuroendocrine function tests and the clinical prognosis during a 5- to 7-year follow-up in patients (n = 29) with a major affective disorder depressed episode. Psychiatric assessment included Research Diagnostic Criteria, the DSM-III, and the Comprehensive Psychopathological Rating Scale (CPRS). The endocrine assessment included the dexamethasone suppression test (DST), nocturnal serum melatonin levels, and thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) administration (A TSH). Several follow-up variables were defined on the basis of individual sick-leave files and psychiatric records. The 16 patients with abnormal DST in the acute state showed significantly increased number of hospitalizations with major depression during the follow-up period. The CPRS global score from the psychopathology rating in the acute state was correlated to the follow-up variables reflecting relapses of major depression.

Effects of illumination on human nocturnal serum melatonin levels and performance

In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36 = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels.

Serum Melatonin in Central Precocious Puberty Is Lower than in Age-Matched Prepubertal Children*

In children a progressive decrease in nocturnal serum melatonin (MT) has been shown with advancing age, suggesting a reduction in the amplitude of the circadian MT curve with maturation. Whether this alteration of MT levels is related to human sexual maturation or occurs independently remains to be elucidated. Also, the impact of gonadal steroids on the MT rhythm remains an open question. We examined 56 patients (51 females and 5 males) with central precocious puberty (52 idiopathic and 4 neurogenic). Patients were studied before and 3, 6, and 12 months after initiation of GnRH analog treatment. Three hundred and thirty-seven endocrinologically normal subjects (190 males and 147 females) served as controls. In all subjects nocturnal serum MT (blood collection between 2300 and 0100 h) was measured with a highly specific RIA. In young patients, aged 1-5 yr, we found significantly lower MT levels than in age-matched controls. Pubertal patients, aged 5-9 yr, displayed nocturnal MT levels in the same range as control subjects approaching normal pubertal age. In contrast to endocrinologically normal children, there was no age-dependent decrease in nocturnal MT in untreated precocious puberty; rather, it appeared that serum MT had already declined in association with the onset of sexual maturation. Although there was a significant difference in weight between patients and age-matched controls, the low MT values in patients 1-5 yr old were only partly explained by the weight difference (P less than 0.0009); their pubertal status also contributed significantly (P less than 0.006). Pituitary-gonadal suppression induced by long term GnRH analog treatment did not result in a return to prepubertal MT levels; rather, nocturnal MT decreased during therapy. The collected data indicate that nocturnal serum MT levels are related to sexual maturation, since serum MT is similar in precocious puberty and normal pubertal children. Since suppression of the pituitary-gonadal axis did not result in increases in nocturnal MT levels in young patients with precocity (i.e. return to age-appropriate levels), the reduction of nocturnal MT with normal puberty is not likely to be dependent on pubertal gonadotropin or sex steroid milieu.

Effect of a 15 minute light pulse on nocturnal serum melatonin levels in human volunteers

Monitoring the daily melatonin rhythm during the course of phototherapy for affective disorders may be beneficial in assessing the efficacy of such treatments. It is therefore of interest to study the effects of the timing, duration, and intensity of bright light pulses on melatonin levels in normal subjects. To examine the effects of a single exposure to a brief burst of bright light on serum melatonin, groups of healthy human volunteers of both sexes were treated with a 15 minute pulse of bright light (350 cd/m2) early in the evening during the winter months. Serial blood samples were collected from each person and the effect of the light pulse on serum melatonin and cortisol levels determined. Melatonin levels were significantly but only transiently suppressed by the light pulse, while cortisol levels were not affected. These results demonstrate that short duration bright light treatments can influence the melatonin rhythm generating system in humans.