Melatonin Secretory Patterns Research Articles

Regulation of adolescent sleep: implications for behavior.

Adolescent development is accompanied by profound changes in the timing and amounts of sleep and wakefulness. Many aspects of these changes result from altered psychosocial and life-style circumstances that accompany adolescence. The maturation of biological processes regulating sleep/wake systems, however, may be strongly related to the sleep timing and amount during adolescence-either as "compelling" or "permissive" factors. The two-process model of sleep regulation posits a fundamental sleep-wake homeostatic process (process S) working in concert with the circadian biological timing system (process C) as the primary intrinsic regulatory factors. How do these systems change during adolescence? We present data from adolescent participants examining EEG markers of sleep homeostasis to evaluate whether process S shows maturational changes permissive of altered sleep patterns across puberty. Our data indicate that certain aspects of the homeostatic system are unchanged from late childhood to young adulthood, while other features change in a manner that is permissive of later bedtimes in older adolescents. We also show alterations of the circadian timing system indicating a possible circadian substrate for later adolescent sleep timing. The circadian parameters we have assessed include phase, period, melatonin secretory pattern, light sensitivity, and phase relationships, all of which show evidence of changes during pubertal development with potential to alter sleep patterns substantially. However the changes are mediated-whether through process S, process C, or by a combination-many adolescents have too little sleep at the wrong circadian phase. This pattern is associated with increased risks for excessive sleepiness, difficulty with mood regulation, impaired academic performance, learning difficulties, school tardiness and absenteeism, and accidents and injuries.

Pulsatile patterns of melatonin secretion in patients with gonadotropin-releasing hormone deficiency: effects of testosterone treatment.

Recently, we have demonstrated that male patients with gonadotropin-releasing hormone (GnRH) deficiency had increased nocturnal melatonin secretion that decreased to normal levels during testosterone treatment. The purpose of the current study was to examine if the abnormally increased melatonin levels in these patients were associated with pulsatile secretory patterns, and, if these were modified during testosterone administration. Characteristics of nocturnal melatonin and luteinizing hormone (LH) secretion were compared in six normal young males, six males with idiopathic hypogonadotropic hypogonadism (IGD), and in six males with constitutional delayed puberty (DP). Patients were examined in the untreated state and following the administration of 250 mg testosterone enanthate/month for 4 months. Serum samples for melatonin and LH levels were obtained every 15 min from 19.00 hr to 07.00 hr in a controlled light-dark environment. Pulse detection and pulse characteristics were determined by the program ULTRA. In comparison with normal controls, untreated IGD patients showed significantly higher pulse frequency, lower relative increments and shorter half-life times for melatonin. Similar findings were observed in DP patients, although statistically of borderline significance. Treatment with testosterone normalized melatonin pulse characteristics in both IGD and DP patients. The secretory pattern of LH release in these patients was characterized by significantly higher relative and absolute increments and shorter half-life time without any significant change in the number of LH pulses. Taken together, these data suggest that melatonin is secreted in a pulsatile pattern in normal adult males and in male patients with GnRH deficiency. The abnormally increased nocturnal melatonin secretion observed in these patients may indicate that the pineal pulse generator is expressing an altered activity pattern within its normal capabilities. Testosterone administration normalized melatonin secretory patterns in IGD and DP patients. The lack of relationship between the pulsatile LH and melatonin secretory patterns suggest an independent signal for the nocturnal pulsatile melatonin and LH secretions.

Circannual Alterations in the Circadian Rhythm of Melatonin Secretion

To determine if a circadian rhythm known to be functionally related to the reproductive axis varies on a circannual basis, we monitored the circadian secretion of melatonin at monthly intervals for 2 years in four ovariectomized, estradiol-implanted ewes held in a constant short-day photoperiod. Prior to the study, ewes had been housed in a short-day (8L:16D) photoperiod for 4 years and were exhibiting circannual reproductive rhythms as assessed by serum luteinizing hormone (LH) levels. Three of the four sheep showed unambiguous deviations from the expected nocturnal melatonin secretion at two different times approximately 1 year apart. Nocturnal rises in melatonin, which usually last the duration of the dark phase, were delayed by 3-14 h or were missing. Altogether, five of the seven melatonin alterations observed in these three ewes occurred during the nadir of the circannual LH cycle. In the remaining ewe, we did not observe an altered melatonin secretory pattern during this period, and this ewe also failed to show a high amplitude circannual cycle of LH. The results provide evidence for a circannual change in the circadian rhythm of melatonin secretion. This alteration in melatonin secretion may serve as a "functional" change in daylength, and thereby may influence the expression of the circannual reproductive rhythm of sheep held in a fixed photoperiod for an extended time.

Circadian Pattern of Plasma Melatonin Concentrations during Four Phases of the Human Menstrual Cycle

The role of melatonin in human reproductive physiology remains obscure. Previous investigations of the nocturnal melatonin secretory pattern during the human menstrual cycle have yielded conflicting results and have been limited by incomplete characterization of the pertinent features of the circadian pattern such as magnitude, duration, or circadian position of the nocturnal increase, by incomplete assessments of ovarian secretion and menstrual cycle phase, or by both. In the present study, the circadian melatonin profile was characterized by obtaining plasma samples at hourly intervals from 10.00 to 17.00 h and at half-hourly intervals from 17.00 to 10.00 h in 10 women during four prospectively estimated menstrual phases: early follicular, late follicular, midluteal, and late luteal. Menstrual phases and ovarian function were confirmed by obtaining daily serum samples for LH, FSH, estradiol, and progesterone during the entire menstrual cycle. Eight women had ovulatory cycles with luteal lengths of greater than 11 days and with determinations of the circadian melatonin pattern during each menstrual phase. Despite gonadal steroid excursions characteristic of ovulatory cycles, consistent variations in plasma melatonin patterns by menstrual phase were not found. Daytime levels were at or below 43 pmol/l in all women and all but 2 women displayed prominent nocturnal elevations. While changes in the circadian pattern of melatonin secretion immediately preceding the LH surge cannot be excluded, the lack of consistent variation by menstrual cycle phase and the absence of clear circadian variation found in 2 women suggests that the secretory profile of melatonin is unaltered by fluctuations in gonadal steroids and that melatonin secretion may not be necessary for menstrual cyclicity to occur.

Maternal melatonin treatment influences rates of neonatal development of meadow vole pups.

Meadow vole dams, housed in a 14L:10D photoperiod were injected daily 3 h before onset of darkness with 10 micrograms melatonin. Treatment during gestation or lactation produced offspring that exhibited altered somatic, testicular, and pelage growth. Gestational melatonin treatment decreased preweaning weight gain, delayed testicular development, and increased pelage growth in offspring, whereas melatonin treatment during lactation increased pelage depth at weaning and increased post-weaning somatic growth. These results suggest that pre- and postnatal maternal melatonin secretory patterns influence postnatal development of photosensitive traits in offspring.

Importance of changing photoperiod and melatonin secretory pattern in determining the length of the breeding season in the Suffolk ewe.

Three groups of ovariectomized Suffolk ewes bearing s.c. Silastic implants of oestradiol were subjected to a 90-day priming treatment of an inhibitory long photoperiod (16 h light/day; 16L:8D). On Day 0 of the experiment, they were moved to stimulatory photoperiods. One control group was transferred to 12L:12D and a second control group was transferred to 8L:16D; both groups remained in those photoperiods to determine the timing of reproductive induction and refractoriness. The experimental group was transferred to 12L:12D on Day 0 and then to 8L:16D on Day 55 to determine whether the further reduction in daylength could delay the development of refractoriness. Reproductive neuroendocrine condition was monitored by serum concentrations of LH and FSH. Both gonadotrophins remained elevated for a longer period of time in the experimental group receiving the second reduction in daylength than in either control group, indicating that the second photoperiodic drop delayed the onset of photorefractoriness. Measurement of 24-h patterns of circulating melatonin suggests that the prolonged stimulation of reproductive neuroendocrine activity in the experimental group resulted from a lengthening of the nocturnal melatonin rise. These findings indicate that refractoriness to an inductive photoperiod can be temporarily overcome by exposure to a shorter daylength, and that the change in duration of the nocturnal increase in melatonin secretion is important in photoperiodic signalling. Thus, in natural conditions, the decreasing autumnal daylength, and the resulting expansion of the nocturnal elevation in melatonin secretion, may be utilized to produce a breeding season of normal duration.

24 hour melatonin secretory pattern in Cushing's syndrome.

The concentrations of plasma melatonin and cortisol were determined every 20 min during a 24 h period in 6 women aged 24 to 45 years with Cushing's syndrome of differing aetiologies (4 adrenal adenomas, 2 adrenal hyperplasia). Melatonin was assayed after chloroform extraction according to the method of Rollag and Niswender (1976). Abnormal melatonin secretory patterns were found in all the patients; 24 h melatonin concentration means varied from 130 to 413 pg/ml and were not significantly higher than the 24 h mean in 4 controls (215 +/- 126 pg/ml). All six subjects however showed a significant increase of melatonin during the day period (302 +/- 109 as compared with controls 129 +/- 65 mg/ml, mean +/- SD; P less than 0.005). No relationship could be found between abnormal melatonin levels and the sexual status of the patients (4 with amenorrhoea, 2 normally menstruating women). An alteration of melatonin secretory pattern is present in Cushing's syndrome, whatever the aetiology. It is suggested that hypercortisolism, by itself, may modify the pattern of melatonin secretion.

Twenty-four hour melatonin secretory pattern in men with idiopathic hemochromatosis

In idiopathic hemochromatosis, iron deposits in endocrine tissue can be associated with hormonal disorders including hypogonadism. We have studied the functional status of the pineal gland in this disease in relation to gonadotrophin levels and cortisol rhythm. Plasma melatonin, luteinizing hormone (LH) and cortisol concentrations were measured by radioimmunoassay every 20 min over a 24 hr period in nine men with idiopathic hemochromatosis aged 36 to 66 years. In six patients a circadian melatonin rhythm was present. The 24 hr means were in the normal range in three patients, and varied below the control values in two patients and above the control values in one patient. These variations seemed unrelated to gonadotrophin status. In the three other patients no plasma melatonin rhythm was observed; two patients with gonadotrophin insufficiency had low melatonin levels, and one with normal gonadotrophin function had high melatonin concentrations. In all cases, the plasma cortisol rhythm was normal. We concluded that the circadian melatonin rhythmicity can be disturbed in some cases of idiopathic hemochromatosis without relationship to the cortisol rhythm and associated endocrine disorders.