Seismic identification of along-axis hydrothermal flow on the East Pacific Rise.

Hydrothermal circulation at the axis of mid-ocean ridges affects the chemistry of the lithosphere and overlying ocean, supports chemosynthetic biological communities and is responsible for significant heat transfer from the lithosphere to the ocean. It is commonly thought that flow in these systems is oriented across the ridge axis, with recharge occurring along off-axis faults, but the structure and scale of hydrothermal systems are usually inferred from thermal and geochemical models constrained by the geophysical setting, rather than direct observations. The presence of microearthquakes may shed light on hydrothermal pathways by revealing zones of thermal cracking where cold sea water extracts heat from hot crustal rocks, as well as regions where magmatic and tectonic stresses create fractures that increase porosity and permeability. Here we show that hypocentres beneath a well-studied hydrothermal vent field on the East Pacific Rise cluster in a vertical pipe-like zone near a small axial discontinuity, and in a band that lies directly above the axial magma chamber. The location of the shallow pipe-like cluster relative to the distribution and temperature of hydrothermal vents along this section of the ridge suggests that hydrothermal recharge may be concentrated there as a consequence of the permeability generated by tectonic fracturing. Furthermore, we interpret the band of seismicity above the magma chamber as a zone of hydrothermal cracking, which suggests that hydrothermal circulation may be strongly aligned along the ridge axis. We conclude that models that suggest that hydrothermal cells are oriented across-axis, with diffuse off-axis recharge zones, may not apply to the fast-spreading East Pacific Rise.

Implications for prediction and hazard assessment from the 2004 Parkfield earthquake.

Obtaining high-quality measurements close to a large earthquake is not easy: one has to be in the right place at the right time with the right instruments. Such a convergence happened, for the first time, when the 28 September 2004 Parkfield, California, earthquake occurred on the San Andreas fault in the middle of a dense network of instruments designed to record it. The resulting data reveal aspects of the earthquake process never before seen. Here we show what these data, when combined with data from earlier Parkfield earthquakes, tell us about earthquake physics and earthquake prediction. The 2004 Parkfield earthquake, with its lack of obvious precursors, demonstrates that reliable short-term earthquake prediction still is not achievable. To reduce the societal impact of earthquakes now, we should focus on developing the next generation of models that can provide better predictions of the strength and location of damaging ground shaking.

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Loss of normal circadian profile of urine excretion in idiopathic restless legs syndrome.

BACKGROUND: This study was performed to elucidate preliminary observations of excessive nighttime urine excretion in idiopathic restless legs syndrome (iRLS). METHODS: Seventeen patients, with normal serum creatinine, blood urea nitrogen, and urate, and 11 healthy controls were examined. We measured excretory renal function parameters (urine volume, osmolarity, sodium, chloride, potassium, calcium, phosphate, microalbumin, aldosterone, creatinine) between 7:00 am and 10:00 pm and between 10:00 pm and 7:00 am. RESULTS: During the nighttime, volume (P=0.006), sodium (P=0.009), and chloride excretion (P=0.001) were significantly higher, and osmolarity (P=0.025) was significantly lower in patients as compared to controls. In comparing daytime to nighttime, controls showed the physiological reduced nocturnal excretion of volume (P=0.009) and chloride (P=0.023), and an increased osmolarity (P=0.026), but patients showed similar excretion rates of these parameters (all differences ns). CONCLUSIONS: These data indicate a loss of normal circadian profile of urine excretion in iRLS. The elevated nighttime excretion, with values similar to those in the daytime, hint at a possibly elevated fluid, sodium, and chloride intake during daytime.

The short term secretion pattern of human serum melatonin indicates apulsatile hormone release.

It is well known that many hormones are secreted in a pulsatile fashion. Changes in pulse frequency and/or amplitude can have severe physiological and pathological consequences. Attempts to assess the short term secretion pattern of the pineal hormone melatonin (MLT) provided inconsistent results. The development of objective statistic- and computer-based pulse detection programs and the advent of more precise and specific MLT assay systems during recent years prompted us to reexamine the short term secretion of the pineal hormone. We investigated 16 healthy volunteers (8 males and 8 females), aged 28.1 +/- 6.7 yr (mean +/- SD). Five-milliliter blood specimens were collected at 10-min intervals from 1900-0900 h (n = 8), 3-min intervals from 2300-0300 h (n = 4), 10-min intervals from 0800-2200 h (n = 2), and 3-min intervals from 1100-1500 (n = 2). The serum MLT concentration in each specimen was measured with a previously described RIA. The sensitivity of the assay varied between 3.0-7.5 pg (0.013-0.033 pmol) MLT/tube. The intrassay variance was assessed on 10 serum pools to which varying amounts of MLT had been added, covering the entire range of the standard curve; the coefficient of variance varied between 16.6-6.1%. The sequence of MLT levels in each subject was examined for the existence of pulses by visual inspection and by the computer programs Pulsar and Cluster. Apart from the circadian rhythm, the three methods did not reveal clear pulses but, rather, continuous release of the pineal hormone during the day and night. We conclude that the pineal hormone MLT is, in contrast to many other hormones, secreted in an apulsatile manner. Very frequent blood sampling may be unnecessary for full characterization of the secretion pattern without loss of information. In addition to the circadian pacemaker, the pineal does not appear to be under the control of the proposed hypothalamic or an intrinsic pulse generator.

Measurement of urinary melatonin: a useful tool for monitoring serum melatonin after its oral administration.

The relevance of measuring urinary melatonin (MLT) for human pineal research is sometimes questioned, and the relationship among serum levels of MLT, urinary excretion of the unmetabolized hormone, and excretion of MLTs main metabolite, 6-hydroxymelatonin sulfate (aMT6s), is still uncertain. We applied a well established RIA for measuring MLT in serum to urine samples, characterized its criteria of performance in this body fluid, and used it for human studies. In 16 adolescents, the endogenous overnight MLT secretion, expressed as the area under the concentration time curve, correlated significantly with the amounts of urinary aMT6s (r = 0.86; P < 0.0001) and urinary MLT (r = 0.70; P = 0.0027) excreted during a 16-h observation period. Oral administration of 3 mg exogenous MLT in 17 healthy volunteers resulted in peak MLT serum levels differing 28-fold among subjects (940-27,240 pg/ mL; range). In this study urinary MLT, but not aMT6s, excretion was associated with blood MLT concentrations (r = 0.76; P = 0.0004 vs. r = 0.02; P = 0.93, respectively). Thus, endogenous MLT production can be assessed accurately by measuring either aMT6s or MLT excretion. After oral application of MLT, however, only measurement of MLT excretion is a reliable marker of serum concentrations. Determination of MLT in urine may prove to be a useful tool for drug monitoring after oral administration of the pineal hormone.

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.

Lack of pineal growth during childhood.

During childhood, serum melatonin concentrations drop by approximately 80%, but the 24-h melatonin excretion is stable. Arrest of pineal growth after the end of infancy has been proposed as one possible mechanism underlying that phenomenon. To test this hypothesis, we reviewed 332 magnetic resonance imaging brain studies, classified as normal, of endocrine-normal children, aged 1 day to 15 yr, and estimated the pineal and pituitary sizes. The pineal was identified in 277 of 332 magnetic resonance imaging studies (83%). The average size (mean +/- SEM) of the pineal gland (transaxial diameter, 5.6 +/- 2.1; midsagittal diameter, 5.0 +/- 2.4; planimetric area, 28.5 +/- 17.8) did not differ with age. A total of 74 of 277 pineals with cysts (26.7%) were found. The occurrence of pineal cysts was equally distributed among the different age groups (chi 2 = 11.6; df = 14; P = 0.7). Ten pineals showed more than 1 cyst (3.6%). The pituitary was identified in 325 of 332 brain images (97.9%). The average pituitary size increased by some 100% from 1 to 15 yr of age [transaxial diameter: F = 2.2; P = 0.005 (by two-way analysis of variance); midsagittal diameter: F = 3.7; P = 0.0001; planimetric area: F = 7.1; P = 0.0001]. The pituitary was slightly larger in females than in males [midsagittal diameter: F = 8.8; P = 0.003 (by two-way analysis of variance); planimetric area: F = 7.9, P = 0.005]. The data presented indicate a lack of a discernible pineal growth after age 1 yr, which contrasts with pituitary development in the same individuals. The data are in agreement with a hypothesis suggesting a growth arrest of the pineal after infancy.

Alterations in nocturnal serum melatonin levels in humans with growth and aging.

The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors.

Diminished prolactin response to thyrotropin and insulin in anorexia nervosa.

Although patients with anorexia nervosa (AN) have a variety of endocrine disturbances, it generally is believed that the PRL response to stimulation is not altered in this disorder. We measured basal serum PRL values and serum PRL values after stimulation either with TRH (200 micrograms/m2) or with insulin (4 IU/m2) in 27 women with AN and 9 normal women. Basal values in anorexic women and normal women did not differ significantly, whereas all stimulation variables (mean PRL stimulation values, maximum PRL values, sum of increments, and area under the stimulation curve) were significantly lower in AN patients than in normal women. Furthermore, after TRH stimulation most of these variables correlated positively with the percentage of ideal body wt of the patients, indicating that the diminished PRL response was wt dependent. This diminished PRL response in the patients may accompany starvation and low estradiol values. Both conditions per se are known for their association with diminished PRL responses. Hence, no hypothesis which posits hypothalamic dopamine excess as the basic disturbance in AN seems justified. Moreover, diminished PRL responses in AN are not consistent with an assumption of hypothalamic dopamine depletion in this disorder.

Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries.

Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

Mutational spectrum of the steroid 21-hydroxylase gene in Austria: identification of a novel missense mutation.

This study attempted an analysis of the mutational spectrum of 21-hydroxylase deficiency in 79 unrelated Austrian patients with classical and nonclassical forms of congenital adrenal hyperplasia and their respective 112 family members. Apparent large gene deletions/conversions were present in 31% of the 158 unrelated congenital adrenal hyperplasia alleles, whereas the most frequent point mutations were intron 2 splice (22.8%), I172N (15.8%), V281L (12%), and P30L (7.6%), in line with the frequencies reported for other countries. In 5 of the 12 congenital adrenal hyperplasia alleles carrying a P30L mutation the aberration is based on a single base substitution, whereas the remaining 7 represent part of a CYP21B conversion (1 allele) or CYP21B/21A hybrid gene (6 alleles), the latter characterized by a junction site before intron 2 as indicated by Southern blot, PCR, and sequence analyses. Previously described mutations were not present in 1.2% of unrelated congenital adrenal hyperplasia alleles, including one female patient presenting with severe genital virilization. Sequence analysis of the complete functional 21-hydroxylase gene revealed an as yet undescribed mutation in exon 10-Arg(426)His, which has not yet been described to represent a common pseudogene sequence. In vitro expression experiments showed the Arg(426)His mutant to exhibit only low enzyme activity toward the natural substrate 17-hydroxyprogesterone corresponding to the degree of disease manifestation in the patient in whom it was found.

Age-related changes in melatonin levels in humans and its potential consequences for sleep disorders.

Prior to three months of age there is little melatonin (MLT) secretion in humans. MLT production then commences, becomes circadian, and reaches its highest nocturnal blood levels between the ages of one to three years. During the remainder of childhood, nocturnal peak levels drop progressively by 80%. In adults, these levels show an additional drop of some 10%, mainly during senescence. The large drop in serum MLT during childhood is probably the result of the increase in size of the human body, despite a constant MLT production after infancy. The additional decline of MLT with higher age may be due to a yet unidentified physiological mechanism accompanying senescence. The biological significance of these MLT alterations remains unknown. Since the discovery of MLT, an immediate sedative action of this hormone has been known. A number of recent studies have demonstrated that MLT indeed exerts a sleep-promoting action by accelerating sleep initiation, improving sleep maintenance, and marginally altering sleep architecture. The potential of MLT in the treatment of insomnia is being explored, and the results are promising. Although in most of these studies pharmacological dosages of MLT have been used, preliminary data suggest that similar effects can also be achieved by physiological hormone concentrations. The latter observation raises the question of whether MLT might be involved in the physiological control of sleep.

Sleep laboratory investigations on hypnotic properties of melatonin.

Melatonin (MLT), a pineal hormone, has some sedative and hypnotic properties. To explore this effect further 20 young, healthy volunteers exposed to artificial insomnia participated in a double-blind, placebo controlled, parallel group design study. They slept in a sleep laboratory for several consecutive nights and were polygraphically monitored and subjected to a battery of psychometric tests and standardized self-report questionnaires each morning. One night all subjects received only placebo (21:00 hours) and on a second night half of them were subjected to placebo and half to MLT. On the later night blood MLT levels were measured. Polygraphic recordings revealed that MLT at bedtime decreased the time the subjects were awake before sleep onset (P less than 0.025), sleep latency (P less than 0.05), and the number of awakenings during the total sleep period (P less than 0.025), and increased sleep efficiency (P less than 0.05). In addition, it decreased sleep stage 1 (P less than 0.05) and increased sleep stage 2 (P less than 0.025). On the morning following the treatment most objective and subjective measures for awakening quality showed a trend towards improvement after MLT. One hour after its oral administration, serum MLT rose to a high pharmacological level (25817 pg/ml; median), but individual peak serum MLT levels varied by a factor of 300.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible behavioral consequences of light-induced changes in melatonin availability.

Melatonin is a hormone secreted at night, in the dark, by the human pineal organ. This nocturnal release of melatonin, in humans and other species, is rapidly suppressed by exposure to sufficiently bright light. In humans, the function, if any, of this circadian pattern of melatonin release has not been determined. In fact, no function has been definitively attributed to the hormone melatonin in humans. In one study, conducted in our laboratory, pharmacologic doses of oral melatonin (240 mg over two hours) were administered to volunteers, and various behavioral parameters were assessed. Melatonin had substantial, but brief, sedative-like effects on mood and performance. Thus it appears that a mechanism exists, whereby light, of sufficient intensity to affect melatonin release in humans, can affect behavior. It can be hypothesized that sufficiently bright light, acting by way of the suppression of melatonin release, can acutely increase alertness or act as a zeitgeber (synchronizer of circadian cycles). The light intensity necessary to suppress melatonin secretion in humans is well above typical indoor lighting conditions, but well below normal outdoor daytime levels of illumination. Therefore, the hypothesis that light may affect behavior or circadian patterns of sleep and waking, if found to be true, could have considerable impact on the design of interior lighting.

Effects of melatonin on human mood and performance.

The function of melatonin, a hormone secreted by the pineal gland primarily at night, has not been definitively established in humans. To determine if pharmacologic doses of melatonin had any behavioral effects it was administered acutely to 14 healthy men. Their mood, performance, memory and visual sensitivity were assessed. Plasma melatonin concentration was assayed as well. Melatonin significantly decreased self-reported alertness and increased sleepiness as measured by the Profile of Mood States and the Stanford Sleepiness Scale self-report mood questionnaires. The effects were brief. Melatonin also affected performance, slowing choice-reaction time but concurrently decreasing errors of commission. Sustained fine motor performance was not impaired after melatonin administration nor were the tests of memory and visual sensitivity that were administered. It is concluded that melatonin, administered orally in pharmacological quantities, has significant but short acting sedative-like properties.

A combination of spastic paraparesis, polyneuropathy and adrenocortical insufficiency-a childhood form of adrenomyeloneuropathy.

This report describes a combination of spastic paraparesis and symmetrical sensory motor polyneuropathy with a pathological response to the ACTH test in the case of a 16 year-old boy and a borderline response to the ACTH test in the case of his 8-year-old sister. Another sister, aged 14, showed only a pathological response to ACTH testing, the neurological status being unremarkable. The EEG was normal in all three children examined. Visually evoked potentials were borderline in the case of the boy and normal in the case of the clinically involved sister. Although on examination by light microscopy the sural nerve proved to be normal, the clinical diagnosis of adrenomyeloneuropathy (AMN) in its juvenile form may be assumed, in view of the clinical symptoms and the evidence of adrenocortical insufficiency revealed by the ACTH test.

Serum melatonin levels: a new neurodiagnostic tool in pineal region tumors?

The pineal hormone melatonin (MLT) is secreted in a circadian rhythm with high serum levels during nighttime and low serum levels during daytime. Several authors have reported an altered secretion pattern of MLT in patients with pineal tumors and have proposed that MLT may be used as a tumor marker. In nine patients, a pineal region tumor was diagnosed by computer-assisted tomography. Before and after surgical removal of the tumor, several day- and nighttime serum samples were collected and MLT concentrations were estimated by radioimmunoassay. Before operation, five patients presented a normal circadian pattern of MLT secretion. In the remaining four subjects, MLT levels were undetectable or at the limit of detection, with no signs of a circadian secretion pattern. Eight patients were reexamined after tumor resection, when all but one had undetectable or very low MLT levels. The remaining subject, with a pineomesencephalic pilocytic astrocytoma, dislocating but not involving the pineal gland, presented a normal circadian secretion pattern of MLT after operation; in this case, tumor resection was possible without damaging the pineal gland. Thus, before operation, MLT deficiency rather than exaggerated serum levels may be used as a marker for pineal tumors that destroy the pineal gland. After tumor resection, serum MLT may serve to demonstrate complete pinealectomy.

Changes in melatonin secretion with age and pubescence.

At the turn of the century, reports on a coincidence of pineal tumors and precocious puberty in man initiated a host of animal experiments. Results of these experiments ultimately revealed a modulating effect on sexual maturation and on gonadal activity in several species, brought about by the pineal hormone melatonin (aMT) and particularly its circadian secretion pattern. In addition, it renewed interest in a possible interaction of the pineal and human sexual function. The introduction of specific and precise aMT assays provided exact evaluation of the circadian aMT secretion pattern in adults. Despite considerable efforts, however, a precise characterisation of this pattern has not yet been achieved in children. In a first step we examined single day- and nighttime serum samples from 280 subjects of all ages. aMT levels were low during early infancy, increased to their highest values around 1 to 3 years and dropped progressively by 75 percent until young adulthood, when they remained fairly stable. Thus, the pattern of aMT levels is the reverse of that of gonadotropin levels or gonadal activity in humans. Whether there is a causal relationship between the activity of the pineal gland and the hypothalamo-pituitary-gonadal axis in humans or whether the described negative correlation in the activity of both glands is purely coincidental remains to be clarified.

Melatonin and adolescent idiopathic scoliosis.

Scoliosis seen in the chicken after pinealectomy resembles adolescent idiopathic scoliosis in man. It has been suggested that in both species, deficiency of the pineal hormone, melatonin, is responsible for this phenomenon. In nine patients with adolescent idiopathic scoliosis and in ten age- and gender-matched controls, the circadian levels of serum melatonin and the excretion of urinary 6-hydroxy-melatonin-sulphate, the principal metabolite of melatonin, were determined. There were no statistically significant differences in the secretion of serum melatonin or the excretion of urinary 6-hydroxy-melatonin-sulphate between the patients and the control group. The hypothesis of melatonin deficiency as a causative factor in the aetiology of adolescent idiopathic scoliosis cannot be supported by our data.