Constant pineal output and increasing body mass account for declining melatonin levels during human growth and sexual maturation
TL;DR: The results show that pineal output barely changes during childhood and adolescence, but there is an age related decrease in SaMT excretion/unit body mass which correlates with an age‐related increase in body mass.
Abstract: Twenty-four-h urine samples, divided into two fractions representing night- and daytime melatonin production, were collected from 115 healthy individuals between the ages of 3 and 80, of known height and weight, and assayed for 6-hydroxy melatonin sulphate (SaMT), a major urinary metabolite of melatonin, by gas chromatography mass spectrometry. The population was divided for analytical purposes into children (boys aged 3-10.99, girls aged 3-9.59), adolescents (males aged 11-17.99, females aged 9.60-17.99), and adults (men and women over 18). The results showed approximately the same excretion over 24 h in all 3 groups but that the night/day ratio was considerably greater in children and adolescents compared to adults (P less than 0.001). However, when the results were expressed as a function of body weight (BW), body surface area (BSA), or creatinine excretion (CE), nocturnal SaMT was higher in children than in adults (P less than 0.001 for all 3 parameters) or adolescents (BW, P less than 0.001; BSA, P less than 0.002; CE, P less than 0.001) and was higher in adolescents than in adults (BW and BSA, P less than 0.001). Children also excreted more during the day than adults (BW, P less than 0.01; CE, P less than 0.001) or adolescents (BW alpha CE, P less than 0.02). Our results show that pineal output barely changes during childhood and adolescence. However, there is an age related decrease in SaMT excretion/unit body mass which correlates with an age-related increase in body mass. We therefore conclude that the decrease in circulating levels of melatonin during growth and sexual maturation is brought about by an increase in body mass.
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TL;DR: A dramatic decrease in the CSF melatonin levels was found in old control subjects and even more so inAD patients, and whether supplementation of melatonin may indeed improve behavioral disturbances in AD patients should be investigated.
Abstract: Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer’s disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 ± 1.1 yr) and in 82 age-matched controls (mean age, 76 ± 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41–80 yr of age [176± 58 (n = 29) and 330 ± 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin level...
330 citations
TL;DR: Future research needs to pinpoint the site(s) of age-related dysfunction so that therapies can be specifically tailored to correct the abnormality in addition to reinforcing any of the intact processes.
244 citations
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..., 2000) and urinary 6hydroxymelatonin (Sack et al., 1986; Young et al., 1988)....
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TL;DR: The present knowledge on the influence of oestrogens on the brain and on the distinctive changes of sleep across the menstrual cycle, during pregnancy and menopause and the interactions between sleep regulation and age-related changes in circadian rhythms are summarized.
220 citations
TL;DR: The hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging is not supported and it is recommended that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.
220 citations
TL;DR: Melatonin and 5-methoxytryptophol (ML) were measured in human pineals (38 controls, 16 subjects with Alzheimer's disease) and time of death had a major influence on the indole concentrations with significantly higher melatonin levels occurring at night (22.00-10.00 h) and significantly higher ML levels occurring during the day (10.
209 citations
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TL;DR: By the usual criteria in endocrinology, the pineal now fulfills all the qualifications of an organ of internal secretion.
Abstract: ONLY A LITTLE over a decade ago, any discussion of the function of the pineal gland included qualifying adjectives such as alleged, supposed, and putative. In the same vein, since it connoted a hormonal function, rather than referring to the pineal as a gland, the phrase pineal organ was usually employed to describe this portion of the epithalamus. However, this is no longer the case, at least in mammals. By the usual criteria in endocrinology, the pineal now fulfills all the qualifications of an organ of internal secretion. Several major discoveries revolutionized ideas concerning the function of the pineal gland. Certainly, as noted frequently in other reviews, the isolation and identification of N-acetyl-5-methoxytryptamine (melatonin), a pineal hormone, from bovine pineal tissue by Lerner et al. (1, 2) provided a strong impetus for subsequent investigations on this sometimes exasperating organ. At least as important as this discovery, however, were the observations that light and darkness govern both ...
1,229 citations
TL;DR: This chapter discusses the strategy of seasonal breeding, the role of photoperiod in timing the annual reproductive cycle, the hypothalamo-pituitary mechanisms that mediatePhotoperiodic regulation of estrous cyclicity, and the photoperperiodic pathway to luteinizing hormone (LH) pulse generator.
Abstract: Publisher Summary This chapter discusses the strategy of seasonal breeding, the role of photoperiod in timing the annual reproductive cycle, the hypothalamo-pituitary mechanisms that mediate photoperiodic regulation of estrous cyclicity, and the photoperiodic pathway to luteinizing hormone (LH) pulse generator. To understand how photic input to the LH pulse generator leads to seasonal changes in gonadal activity, the sequence of endocrine events that normally leads to ovulation during the estrous cycle of the ewe must be considered. These preovulatory events occur during a 2–3 day follicular phase and include a precipitous drop in progesterone, a progressive rise in tonic LH secretion, a sustained increase in estradiol secretion, and the LH surge. The pivotal step in this sequence is the sustained increase in tonic LH secretion. A great deal of insight has been gained into the complex interplay between the neural and endocrine response systems that underlie the seasonal reproductive process in the short-day breeding ewe. Specifically, light cues activate retinal photoreceptors and are transmitted via a monosynaptic tract to the suprachiasmatic nuclei of the hypothalamus. After interacting with the circadian system, the photic information is relayed to the pineal gland that transduces the neural message into a hormonal signal in the form of a circadian rhythm of melatonin secretion. The pattern of this melatonin signal, which is interpreted as inductive or suppressive, sets the frequency of the LH pulse generator and determines the capacity of this neural oscillator to respond to the negative feedback action of estradiol. The resulting changes in the episodic pattern of gonadotropin secretion, in turn, dictate whether or not estrous cycles can occur.
601 citations
TL;DR: Serum melatonin concentrations were determined by RIA in 81 healthy humans, aged 1–92 yr and the results suggest that serum melatonin may be secreted under the agerelated neural control of pineal metabolism.
Abstract: Serum melatonin concentrations were determined by RIA in 81 healthy humans, aged 1–92 yr. The daytime (0900–1100 h) serum levels of melatonin decreased progressively with advancing age. No sex difference was noted. The nocturnal rise of serum melatonin in the aged group was significantly reduced compared with that in the young group. These results suggest that serum melatonin may be secreted under the agerelated neural control of pineal metabolism.
377 citations
TL;DR: A simple and rapid RIA is described for 6-hydroxymelatonin sulfate in human plasma and urine that would allow noninvasive study of pineal function, applicable in particular to pediatric and long term circadian rhythm studies.
Abstract: An assessment of the rhythmic characteristics of melatonin secretion in man and other species requires the determination of 24-h secretion profiles. Measurement of a major excreted metabolite would allow noninvasive study of pineal function, applicable in particular to pediatric and long term circadian rhythm studies. This report describes a simple and rapid RIA for 6-hydroxymelatonin sulfate in human plasma and urine. Physiological studies revealed that both plasma and urinary levels of 6-hydroxymelatonin sulfate were closely related to plasma melatonin, and that the urinary 24-h rhythm was abolished by the beta 1-adrenergic anagonist atenolol.
353 citations
TL;DR: Nocturnal plasma concentrations of luteinising hormone measured at various stages of puberty tended to vary inversely with those of melatonin, and past difficulties in demonstrating a relation between gonadal maturation and human pineal function may have reflected the use of insufficiently sensitive or specific melatonin assays, or serum sampling only during daytime.
278 citations