Parallel nocturnal secretion of melatonin and testosterone in the plasma of normal men

Abstract: Differences and similarities in the temporal organization of hormone secretion in plasma reflect the activity of CNS pacemakers. One aspect of this activity, the temporal synchronization of the secretion of different hormones is still poorly understood. We report the analysis of melatonin and testosterone plasma concentrations during two nights in 6 normal healthy young men. Blood was collected every 20 min between 2040 and 0640. Plasma testosterone concentrations increased by 1.5- to 2-fold during the second part of the night, and melatonin by 2.5- to 4-fold. In each subject, the individual temporal pattern of melatonin was quite stable over the two nights of sampling, while testosterone profiles showed fluctuations. There was a high degree of parallelism in these two hormones nocturnal secretion. These results, together with previous studies, suggest that melatonin might entrain the nocturnal secretion of testosterone.     

Characterization of nocturnal ultradian rhythms of melatonin in children with growth hormone-dependent and independent growth delay

To assess the existence of a possible nocturnal ultradian rhythm of melatonin in children, we analyzed 28 pediatric patients (mean age, 9.08 +/- 2.2 yr) with GH-dependent and GH-independent growth delay. Plasma melatonin was measured by RIA in children sampled every 30 min between 2100-0900 h. Statistical analysis consisted of cluster analysis to examine the presence of peaks and troughs. The pattern of melatonin levels was related to the cause of growth delay, although the means of the nocturnal concentrations of melatonin were similar in all children. Interestingly, children with a GH deficit showed a nearly normal melatonin profile, whereas children with normal GH values but abnormal growth displayed atypical profiles of melatonin. The results also prove the existence of an ultradian rhythm of melatonin in most of the patients studied. The ultradian rhythm of melatonin in children was characterized by irregular interburst intervals, thus differing from the rhythm previously described in adults that had an almost constant pulse frequency. Moreover, the existence of low and high melatonin producers was revealed in the study, a feature unrelated to the cause of growth delay. The group of children with a GH deficit showed the lowest values of integrated melatonin production and of the area of peaks and troughs. These results prove that children exhibit an ultradian rhythm of melatonin like that in adults. Whereas it is not clear whether the episodic production of melatonin is required for its biological actions, the existence of irregular pulses may reflect endocrine influences at this age and/or the immaturity of the intrinsic pulse generator.     

Nocturnal melatonin and luteinizing hormone rhythms in women with hyperprolactinemic amenorrhea

Abstract: To examine the role of melatonin in pathological hyperprolactinemia we compared untreated young females (N = 5) with hyperprolactinemic amenorrhea owing to pituitary microadenoma to healthy female controls (N = 6). Serum samples for melatonin, prolactin, and luteinizing hormone (LH) concentrations were obtained every 15 min from 1900 hr to 0700 hr in a controlled light-dark environment with simultaneous sleep recordings. The mean (±SD) light-time period, dark-time period, and the integrated nocturnal melatonin secretion values (area under the curve, or AUC) in patients (51 ± 11 pmol/L, 157 ± 33 pmol/L, and 102 ± 19 pmol/min-L × 10³, respectively) were similar to the values obtained in controls (79 ± 39, 165 ± 44, 111 ± 31, respectively). The onset of the nocturnal melatonin rise, peak level, and peak time were similar in the two groups. A significant nocturnal prolactin rise was observed in patients (112 ± 9 vs. 65 ± 11 μg/L, P < 0.006) and controls (19 ± 2 vs. 10 ± 3 μg/L, P < 0.006). The time of prolactin peak was similar in patients and controls (0424 ± 3: 36 vs. 0350 ± 2: 21) and paralleled that of melatonin (0354 ± 1: 46 vs. 0337 ± 1: 30). The mean ± SD light-time period, dark-time period, and the AUC values of LH were similar in patients and controls. The number of LH pulses in patients (7.2 ±1.9 per 12 hr) were not different from those in controls (7.7 ±2.1). The LH pulse interval was 100 ± 22 min in patients compared with 94 ± 23 min in controls. The mean (±SD) nocturnal estradiol (E2) levels were significantly lower in patients (84 ±15 pmol/L) than in controls (224 ± 77) (P < 0.005). Analysis of LH and melatonin secretory profiles revealed significant pulses for both hormones. No significant relationship was observed between the LH and melatonin pulses. However, a negative correlation between LH pulse amplitude and the number of melatonin pulses (P < 0.04) and a positive correlation between LH amplitude and duration of melatonin pulses (P < 0.04) were observed. Taken together, these data suggest that the suppression of normal ovarian cycles in women with hyperprolactinemic amenorrhea owing to pituitary microadenoma may be mediated by blocking of gonadotropin action by prolactin at the ovarian level; yet it remains possible that chronically elevated prolactin might prevent the LH surge and thus lead to amenorrhea. Pulsatile melatonin secretion is unaltered in these patients, and the frequent occurrence of amenorrhea in this population is not mediated by melatonin.     

Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men.

Melatonin levels exhibited a day-night rhythm with highest levels at night. Nocturnal plasma melatonin concentrations were unrelated to sleep stages, whereas secretion of GH was temporally related to slow wave sleep. Levels of corticotropin rose in the later sleep cycles. We found no relationship between endogenous nocturnal melatonin and adenohypophyseal hormone levels. The results indicate that in young men nocturnal levels of melatonin are controlled separately from those of LH, PRL, corticotropin, and GH.     

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin in women

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin were studied in 11 normal cycling women during their follicular phases. Blood samples were obtained via an indwelling venous catheter every 10 min. for 2.5 hours starting at 9:30 and 21:30h. For the blood samplings taken at night, six women were kept in a dark room and were permitted to sleep. Their blood samples were obtained using a flashlight (5-10 lux) without their rest being disturbed. However, the other five women were exposed to light (3,000 lux at eye level) and awakened from 22:40 to 24:00h. Plasma melatonin concentrations in the morning decreased from 48.7 +/- 11.6 pg/ml at 9:30h to 24.7 +/- 4.0 pg/ml at 12:00h. On the other hand, plasma melatonin concentrations at night increased from 65.4 +/- 9.6 pg/ml at 21:30h to 138.2 +/- 28.6 pg/ml at 24:00h. The pulsatile LH secretion was changed from the type of "high frequency, low amplitude" in the morning to the type of "low frequency, high amplitude" at night. Nocturnal FSH concentrations were lower than diurnal ones, but nocturnal prolactin concentrations were higher than diurnal ones. Nocturnal concentrations of melatonin were suppressed 40 min. after the light exposure (from 117.4 +/- 11.4 pg/ml at 22:40h to 74.6 +/- 13.9 pg/ml at 23:20h). On the the other hand, the light exposure increased plasma prolactin concentrations from 10.9 +/- 4.1 ng/ml at 22:40h to 17.0 +/- 4.4 ng/ml at 22:50h, maintained those higher levels for 20 min. and decreased them gradually after 23:20h. With the light exposure, mean values of nocturnal LH concentrations were increased from 11.9 +/- 1.5 mIU/ml before exposure to 14.2 +/- 1.8 mIU/ml after exposure, and those of FSH were also increased from 5.9 +/- 0.4 mIU/ml to 6.3 +/- 0.4 mIU/ml. These results showed that the secretion of melatonin, as well as LH, FSH and prolactin had daily rhythms and that melatonin and prolactin showed different responses to light exposure, suggesting different control mechanisms for the secretion of those two hormones.     

Seasonal changes in melatonin concentrations in female Iberian red deer (Cervus elaphus hispanicus)

In deer, most of the earlier investigations on pineal function examined the effects of artificial photoperiods or the administration of melatonin to manipulate reproduction. However, endogenous melatonin rhythms have not been studied in red deer. Thus, we monitored seasonal changes in plasma melatonin concentrations in 16 adult female Iberian red deer living in outdoor enclosures. Blood was sampled on the day of each seasonal change every 3-4 hr overnight and 1 hr before and after sunset and sunrise. In addition, in six of the previous hinds, blood sampling during the hour prior and after sunset and sunrise was collected every 20 min. Significant differences were found both in amplitude and duration of the nocturnal plasma melatonin profiles in the four seasonal changes (P < 0.01). The nocturnal mean level of melatonin, the duration of nocturnal secretion levels and maximal concentrations were significantly higher at the winter solstice than in summer solstice or equinoxes (P < 0.05). Moreover, the mean overnight concentrations were significantly higher at the spring equinox and winter solstice than during the summer solstice and autumn equinox (P < 0.05). A pronounced elevation from low levels was recorded 1 hr after sunset, remained elevated during the hours of darkness and declined to low levels 1 hr after dawn. Concentrations close to sunrise were higher than those near sunset at all changes of season (P < 0.05). These results show for the first time in red deer that the pineal gland of the adult female is highly responsive to both daily and seasonal changes in natural environmental illumination, although overnight levels lasted longer than the photoperiodic night is all cases, particularly at the winter solstice.     

Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia

Abstract: Polysomnographic sleep patterns and melatonin secretion were investigated in 10 patients (age: 41.3 ± 9.5 years) who suffered from chronic primary insomnia and complained predominantly about difficulties in maintaining sleep and in five healthy controls (age 27.2 ± 0.7 years). Nocturnal plasma melatonin concentrations were obtained hourly, measured by direct radioimmunoassay and statistically compared between insomniacs and controls with age as a covariate. Plasma melatonin levels in the patient group tended to begin increasing earlier in the evening and were significantly (P ± 0.01) lower during the middle of the night (peak value 82.5 ± 26.5 pg/ml) than in the healthy controls (peak value 116.8 ± 13.5 pg/ml). Among the patients, the most severely reduced nocturnal plasma melatonin levels were found in those patients with a history of sleep disturbance lasting for longer than five years (N = 6; age 41.8 ± 11.7 years; duration 15.3 ± 5.9 years; peak value 72.1 ± 25.0 pg/ml); whereas those chronic insomniacs affected for fewer than five years had relatively higher nocturnal levels (N = 4; age 40.6 ± 6.5 years; duration 3.8 ± 1.5 years; peak value 98.2 ± 23.9 pg/ml). These results show that the circadian rhythm of melatonin secretion is disturbed in patients with chronic primary insomnia, and that the nocturnal plasma melatonin secretion is increasingly more affected the longer the patients are unable to maintain a regular sleep pattern.     

Lack of an acute modulatory effect of melatonin on human nocturnal thyrotropin and cortisol secretion

Using a recently developed model for investigating the neuroendocrine role of melatonin in man, we studied melatonin's effect on the nocturnal secretion of thyrotropin and cortisol in 17 normal male volunteers. The model consists of sleep in the dark and all-night sleep deprivation in conditions of: bright light with and without a melatonin infusion, and dim light. We have improved our infusion paradigm so that levels of melatonin during infusion are now indistinguishable from those occurring during sleep in the dark or dim light sleep deprivation. Sleep deprivation per se raised TSH levels compared to normal sleep. However, the three conditions of sleep deprivation could not be distinguished from each other, which suggests that the suppression of TSH by sleep (or the stimulation of TSH by sleep deprivation) is not mediated by melatonin. Cortisol secretion was unaffected by sleep deprivation regardless of melatonin's presence or absence. However, a difference in the pattern of secretion of cortisol in the sleep condition in the early morning (compared to the sleep deprivation conditions) was noted. These data do not implicate melatonin in the acute regulation of TSH or cortisol in normal man. These data also provide a method of melatonin infusion that replicates the pattern and levels seen in sleep.     

Increased melatonin concentrations in children with growth hormone deficiency

A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1-16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below -2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children.     

Melatonin treatment for age-related insomnia

Older people typically exhibit poor sleep efficiency and reduced nocturnal plasma melatonin levels. The daytime administration of oral melatonin to younger people, in doses that raise their plasma melatonin levels to the nocturnal range, can accelerate sleep onset. We examined the ability of similar, physiological doses to restore nighttime melatonin levels and sleep efficiency in insomniac subjects over 50 yr old. In a double-blind, placebo-controlled study, subjects who slept normally (n = 15) or exhibited actigraphically confirmed decreases in sleep efficiency (n = 15) received, in randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3.0 mg) orally 30 min before bedtime for a week. Treatments were separated by 1-wk washout periods. Sleep data were obtained by polysomnography on the last three nights of each treatment period. The physiologic melatonin dose (0.3 mg) restored sleep efficiency (P < 0.0001), acting principally in the midthird of the night; it also elevated plasma melatonin levels (P < 0.0008) to normal. The pharmacologic dose (3.0 mg), like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia and caused plasma melatonin to remain elevated into the daylight hours. Although control subjects, like insomniacs, had low melatonin levels, their sleep was unaffected by any melatonin dose.     

Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction. RESULTS: Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3-3.1)%, but it increased by 0.5 (-1.0-1.9)% in group 2, mean difference (95% CI), -2.1 (-4.0 to -0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0-25.0)% in group 1 but rose by 7.7 (-9.7-28.4)% in group 2, mean difference (95% CI), -19.6 (-35-0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.     

Seasonal alterations in circadian melatonin rhythms of the European wild boar and domestic gilt

The aims of the present study were: 1) to determine if the European wild boar exhibits a circadian pattern of melatonin secretion under its natural light environment; 2) to compare this pattern with the pattern in domestic pigs reared under the light environment typical for domesticity; and 3) to determine if there are seasonal alterations in melatonin rhythms. Four to six young, pure-bred, European wild boars and four to six cross-bred (Yorkshire x Finnish Landrace) domestic gilts were sampled at 2-hr intervals for 48 hr at the spring/autumn equinoxes and summer/winter solstices. Samples were obtained via saphenous arterial catheters from the wild boars and via ear vein catheters from the domestic gilts. The ambient light intensity was recorded simultaneously with sampling both outdoors and indoors. Following ether extraction, the serum samples were assayed for melatonin using a commercial RIA (Bühlman). All the experimental animals exhibited a distinct circadian pattern in melatonin secretion, with high concentrations occurring during the scotophase. There was no difference in scotophase melatonin response between the wild boars and domestic gilts in any season in terms of mean melatonin concentration or peak value. The mean duration of increased melatonin secretion (more than two standard deviations over a mean photophase concentration) in 24 hr in the wild boars in spring, summer, autumn and winter, was 10, 6, 11 and 17 hr, respectively, and in the domestic gilts, 9, 8, 12 and 11 hr, respectively. These results demonstrate the existence of circadian rhythm in melatonin secretion in both the European wild boar and domestic pig. In both groups, the duration of secretion is subject to seasonal alterations. The results suggest no difference in photoperiodic-melatonin transduction between the European wild boar and domestic pig whether due to altered genotype or reduced light environment.     

Seasonal variations in the nycthemeral rhythm of plasma melatonin in the camel (Camelus dromedarius)

Seasonal changes in the pattern of plasma melatonin were investigated in two groups of camels (Camelus dromedarius): 11 adult and six young camels. Animals were subjected to the outdoor conditions of a desert environment. Blood samples were taken at regular intervals of about 3 hr (added to particular samples at 1 hr before then 30 min and 1 hr after sunset, and 1 hr before and 1 hr after sunrise) for 24 hr at both solstices and equinoxes of the year. The plasma melatonin levels steeply increased soon after sunset and remained elevated throughout all the night. Then, melatonin concentrations progressively declined shortly before sunrise and returned to daytime basal levels 1 hr later. There was no seasonal variation in the amplitude or in the offset of the melatonin peak or in the daytime basal levels. The onset of the nocturnal peak was delayed by 2 hr in June at the summer solstice (P < 0.05), which can be related to the changes in night length between the two solstices. A significant effect of age was observed in all seasons. Melatonin levels were higher in the young camel group (fall equinox: P < 0.001; spring equinox: P < 0.01; winter solstice: P < 0.01; summer solstice: P < 0.05). The pattern of melatonin secretion in the camel showed a significant seasonal variation parallel to the photoperiodic changes of the year. The observed decline of melatonin levels during an extra-light pulse in the middle of the night indicates the light control of melatonin synthesis. It is not yet known if, in this low latitude desert region, the seasonal breeding period of the camel is cued by the photoperiod. The data obtained, however, clearly demonstrate that the camel has the capacity to follow and to integrate photoperiodic changes through melatonin changes.     

Circadian secretion patterns of melatonin after major surgery

Abstract: Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.     

Nocturnal secretory patterns of melatonin, luteinizing hormone, prolactin and Cortisol in male patients with gonadotropin-releasing hormone deficiency

Abstract: To clarify whether disorders of gonadotropin releasing hormone (GnRH) deficiency are associated with altered melatonin and pituitary hormones secretory patterns, we studied male patients with hypogonadotropic hypogonadism (IGD; n = 6), delayed puberty (DP; n = 7) and age-matched pubertal controls (n = 7). Serum samples for the determination of melatonin, luteinizing hormone (LH), prolactin and Cortisol levels were obtained at 15 min intervals from 1900 to 0700 in a controlled light-dark environment, complete bed-rest and fasting with simultaneous sleep recordings. Mean (± SD) dark-time melatonin levels were significantly higher in IGD (286 ± 26 pmol/L) and DP (205 ± 44 pmol/L) compared with 178 + 64 pmol/L in controls ( P < 0.003). So were the mean (± SD) peak melatonin levels (453 ± 63, 346 ± 106 and 292 ± 96 pmol/L) in IGD, DP and controls, respectively ( P < 0.03). Integrated nocturnal melatonin (AUC) values were also higher in IGD and DP (184 ± 15 and 134 ± 28 pmol/min/L × 10³) compared with 116 ± 42 pmol/min/L × 10³ in controls ( P < 0.003). The time of onset of the nocturnal melatonin rise was observed earlier in IGD and DP patients as compared to controls. No correlations were found between melatonin and LH levels, between melatonin and prolactin levels, or between melatonin and Cortisol levels. These data indicate that melatonin secretion is enhanced in male patients with GnRH deficiency. The lack of correlation between melatonin and LH suggest that circulating gonadal steroids, rather than LH, modulate melatonin secretion in a reverse fashion.     

The hypothermic effect of melatonin on core body temperature: Is more better?

Abstract: Recent studies have shown that melatonin is both hypnotic and hypothermic at physiological levels. Indeed, the hypnotic effect may be mediated via the hypothermic action. If this is the case, it is important to explore the dose-response relationships for the thermoregulatory effects of melatonin. Four groups of eight healthy adults (n = 32), aged between 18 and 38, each underwent two 12-hr bedrest protocols in which core body temperature (CT) and plasma melatonin levels were measured concurrently between 0800 and 2000 hr. For each group, subjects ingested either sucrose placebo or a 0.1, 0.5, 1.0, or 5.0 mg melatonin capsule at 1600 hr in a double-blind counterbalanced cross-over design. Melatonin was absorbed rapidly, with peak levels being reached after 1 hr at all dose levels. Mean peak plasma melatonin levels increased from physiological to pharmacological levels in a dose-dependent manner. Elimination for all dose levels was rapid, with mean plasma half-lives between 33 and 47 min. At the lower doses the mean drop in CT was between 0.05 and 0.15°C and took between 2 and 3 hr. At the higher doses (1.0 and 5.0 mg), CT fell by 0.25–0.3°C within 30–60 min following ingestion and at the highest dose (5 mg) remained suppressed for the duration of the study. While the magnitude and duration of the drop increased in what appeared to be a dose-dependent manner, it is unlikely that this relationship reflects a simple dose-response curve. There was considerable variability in plasma profiles following administration, particularly at the two lowest doses (0.1 and 0.5 mg). The lower mean drop in CT probably reflects the lower proportion of subjects achieving physiological plasma levels, and therefore a hypothermic effect, at the two lowest doses. If melatonin is to be used to improve sleep onset and maintenance by lowering CT, doses between 1.0 and 5.0 mg appear to be the lowest that produce a consistent drop in CT across all subjects.     

Nocturnal continuous infusion of growth hormone (GH)-releasing hormone results in a dose-dependent accentuation of episodic GH secretion in normal men

Fluctuations in plasma GH levels have been found in patients with acromegaly who have continuously elevated levels of ectopically produced GH-releasing hormone (GHRH). Likewise, plasma GH fluctuations have been found in normal subjects receiving continuous GHRH infusions. We report the effects of two doses of GHRH, administered by constant infusion, on nocturnal GH secretion in six normal young men. Each received, in random order, 2.5 ng/kg X min GHRH, 15 ng/kg X min GHRH, and 0.15 M NaCl. During both GHRH doses, a highly significant increase in total nocturnal GH secretion was found (P less than 0.001) as well as an increase in GH secretion during different periods of the night. Nocturnal GH secretion was episodic during the GHRH infusions, with an increase in the number and magnitude of the peaks compared to those during the NaCl infusion. Plasma immunoreactive GHRH concentrations plateaued at 1 h during the high dose and at 3 h during the low dose GHRH infusion. Sleep parameters, including total sleep time, sleep latency, and duration and timing of the different sleep stages, were not affected by GHRH infusions. We conclude that GHRH, continuously infused, increases nocturnal GH secretion according to the dose, while the episodic pattern of GH secretion is maintained.     

Effect of estradiol on plasma melatonin levels

Melatonin levels were determined in plasma samples obtained at 15 minute intervals during a 4-hour period (08:00 - 12:00 hours) from a normal adult male on 5 consecutive days. On days 1, 2, and 3, the subject was given estradiol valerate (E2) 10 micrograms/kg at the end of each sampling period. An episodic pattern of melatonin secretion was found. Post E2 mean estradiol levels per 4 hours increased and mean melatonin and testosterone levels per 4 hours decreased significantly. A decrease in melatonin levels post E2 is the reverse of the response expected based on nonhuman animal experimental data.     

Looking for the keys to diurnality downstream from the circadian clock: role of melatonin in a dual-phasing rodent, Octodon degus

Melatonin is an essential component for circadian system function, whose daily plasma secretory rhythm is driven by the suprachiasmatic nucleus (SCN), contributing to the communication of temporal messages from the central circadian clock to all cells. Melatonin secretion peaks in the dark, regardless of whether animals are diurnal or nocturnal. To date, the precise mechanisms that explain how the circadian system is configured as nocturnal or diurnal remain unknown. The present study examines mid-day and midnight melatonin plasma levels and the influence of exogenous melatonin on the circadian system phasing of Octodon degus, a diurnal rodent, which exhibits nocturnal and diurnal chronotypes when free access to a wheel is provided. Plasma levels of melatonin were determined by RIA in blood samples taken from the jugular vein at mid-light (ML) and mid-dark (MD). Melatonin (0.5 mg/kg b.wt.) was orally administered in their drinking water for 30 days, 2 hr before the onset of darkness. The results showed that plasma melatonin levels and their qualitative effects, hypothermia and improved synchronization with no modification in the 24-hr wheel running activity (WR), were similar in both nocturnal and diurnal degus. Furthermore, melatonin can be used to improve the impaired circadian rhythmicity observed in aged animals, with no rebound effect after ceasing the treatment. It is concluded that plasma melatonin levels and the differential responses to melatonin do not seem to be responsible for nocturnal and diurnal chronotypes, and thus other mechanisms upstream, within, or downstream from the SCN should be investigated.     

Modulation of plasma melatonin concentrations by changes in posture

Abstract: Posture change from a lying position to a standing position results in a decrease in plasma volume, which leads to an increase in plasma constituents, especially that of proteins and blood constituents bound to them. The aim of the present study was to investigate the physiological effects of postural changes on plasma nocturnal melatonin concentrations in healthy human volunteers. The study was divided into four stages. During stage one, subjects were seated from 21.00 hr to 01.00 hr. In stage two, subjects were lying at ground level from 21.00 hr to 01.00 hr. In stage three, subjects were is a sitting position from 2100 hr to 2300 hr and then in a standing position from 23.00 hr to 24.00 hr, and back to the sitting position from 24.00 hr to 01.00 hr. In the final stage, subjects were in a lying position from 21.00 hr to 23.00 hr and then in a standing position from 23.00 rh to 24.00 hr and back to the lying position from 24.00 hr to 01.00 hr. AUC analysis showed significant differences between sitting and lying positions ( t =2.84; P <0.05; df=5), with higher melatonin levels associated with the sitting position (mean difference in peak concentration of 17.1 pg/ml). Furthermore a change in posture from the lying to the standing position produced a statistically significant increase in melatonin concentrations (final stage) ( t =−3.37; P <0.05; df=5) (mean difference in peak concentration of 28.5 pg/ml). No differences were found with a change in posture from a sitting to a standing position. The hemoconcentration and hemodilution associated with posture changes may play a role in altering plasma protein bound hormones such as melatonin.