Showing papers in "Journal of Pineal Research in 1985"
TL;DR: The data suggest that immunoreactive melatonin concentrations in the Harderian glands of hamsters are controlled by testosterone or its derivatives; these same factors also control the male or female character of these glands.
Abstract: Throughout a 24-h period, immunoreactive melatonin concentrations in Harderian glands of female golden hamsters were approximately 200 pg/mg protein with a significant decline to 80 pg/mg protein only at about 0600, 2 h after light on. Concentrations in glands of males are diurnally constant and low (ca. 20 pg/mg protein). Castration increases immunoreactive melatonin in glands of males to female levels. While blinding alone had no effect, it did prevent the castration-induced increase. Lower conentrations were measured in glands of blinded or blinded ovariectomized females but this decrease was not significant. These data suggest that immunoreactive melatonin concentrations in the Harderian glands of hamsters are controlled by testosterone or its derivatives; these same factors also control the male or female character of these glands.
86 citations
TL;DR: The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4‐h intervals throughout a 24‐h period in elderly men with different types of prostate tumors as well as in young men.
Abstract: The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean-cosinor method, and linear correlation coefficients between the five hormones were calculated for each group. Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty-four-hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.
76 citations
TL;DR: It is hypothesized that the second, circadian, factor may be mediated in part by secretion of the pineal hormone melatonin, which is largely confined within the daily dark period when most humans sleep.
Abstract: The likelihood that someone will feel sleepy or will actually fall asleep [Dement and Carskadon, 19821 seems to depend on two temporal fxtors: the subject’s recent sleep history (that is, the quality and duration of the sleep obtained during the prior nights, and the number of hours since termination of the last sieep period) and the time of day or night that these behaviors are being assessed (that is, the point within the subject’s circadian sleep-wakefulness cycle). The first factor could reflect accumulation or depletion of a brain constituent that is removed or replenished by the act of sleeping [Krueger et al., 19821. We hypothesize that the second, circadian, factor may be mediated in part by secretion of the pineal hormone melatonin. Melatonin’s secretion in man is largely confined within the daily dark period [Lynch et al., 1975; Weitzman et al., 1978; Pelham et al., 19731, when most humans sleep, and is rapidly suppressed if, during the night, the individual is exposed to light of sufficient intensity [Lewy et al., 19801. Episodes of nocturnal wakefulness reportedly are followed by short periods of increased melatonin secretion coincident with falling back to sleep [Birkeland, 19821. Exogenous and, presumably, endogenous melatonin readily gain access to the brain from blood or CSF, and thereafter accumulate in brain regions (like the brain stem) known to participate in sleep onset [Wurtman et al., 1964; Jouvet, 19731. Administration of melatonin to rats affects brain
51 citations
TL;DR: The data are interpreted as suggesting that separate mechanisms regulate serum melatonin and serum NAS is response to environmental stimulation and that under appropriate control conditions melatonin from the pineal is very responsive to environmental stimuli, in a manner similar to that of pituitary hormones.
Abstract: The effects of housing condition and type of stimulation on serum melatonin and N-acetylserotonin (NAS) were investigated. Male rats were housed under a 12/12- hour light-dark cycle, with ad libitum food and water, either individually or in groups of four. At the start of the light phase, separate groups were sacrificed at rest or subjected for 3 minutes to the stimulation of cold water, noise, novel environment, or ether vapour and then decapitated at 0, 5, 15, 30 or 60 minutes after the end of stimulation. Melatonin was measured by a modified radioimmunoassay and NAS by a specific radioimmunoassay. Melatonin levels responded to stimulation with an increase, while NAS levels responded with a decrease. Housing condition had no effect on hormone response. However, the pattern of response for each of the two hornomes differed greatly among the stimuli. For melatonin, cold water was the most potent stimulus, followed by noise, novel environment, and ether. NAS responded most to ether, fleetingly to cold, and in a bimodal manner to noise. The data are interpreted as suggesting that separate mechanisms regulate serum melatonin and serum NAS is response to environmental stimulation and that under appropriate control conditions melatonin from the pineal is very responsive to environmental stimuli, in a manner similar to that of pituitary hormones.
51 citations
TL;DR: Rat and hamster pineal glands were used in binding studies to characterize their β‐adrenoceptors with a new specific antagonist ligand, iodocyanopindolol, and results indicate that a selective decrease in catecholamine synthesis in the hamsterpineal does not change the β‐ adrenoceptor density or affinity.
Abstract: Rat and hamster pineal glands were used in binding studies to characterize their beta-adrenoceptors with a new specific antagonist ligand, iodocyanopindolol. The receptors were saturable, and the ligand was selective and demonstrated stereospecificity for both species. The rat pineal had a 20-fold greater density of beta-adrenoceptors, while the affinity was one-third that of the hamster pineal. utilizing this radioligand, we examined the effects of decreased sympathetic input to the pineal on beta-adrenergic receptors in both species. Decreased noradrenergic input to the pineal gland of the hamster was accomplished by superior cervical ganglionectomy, or by exposing the animals to continuous light for 36 hours. Parallel studies were conducted with hamster pineal gland in which catecholamine synthesis was measured. The results indicate that a selective decrease in catecholamine synthesis in the hamster pineal does not change the beta-adrenoceptor density or affinity. In contrast, a concomitant increase in beta-adrenoceptor density but not affinity occurs in the rat pineal gland after similar decreased sympathetic input.
45 citations
TL;DR: The blood melatonin rhythm precisely reflected the rhythms shown by the pineal and eyes, supporting the idea that the blood rhythm is a result of melatonin secretion by both the eyes and pineal.
Abstract: The profile of melatonin in the eyes, pineal, and blood of Japanese quail was assessed in birds held under LD 16:8 and LD 6: 18 photoperiods. Melatonin levels in all three tissues showed a robust daily rhythm with higher levels occurring at night. The amplitude of the rhythm was depressed and its duration lengthened on LD 6: 18 relative to LD 16:8. The blood melatonin rhythm precisely reflected the rhythms shown by the pineal and eyes, supporting the idea that the blood rhythm is a result of melatonin secretion by both the eyes and pineal.
The ocular melatonin rhythm continued after sectioning of the optic nerve, was reentrainable to a shift in the phase of the LD cycle, and persisted for at least 2 days in constant darkness. It was concluded that either (1) an intraocular circadian clock drives the ocular melatonin rhythm, or (2) an extraocular clock drives the ocular melatonin rhythm via a route other than the efferent innervation (which enters the eye via the optic tract).
44 citations
TL;DR: It seems that under very long photoperiods, the N‐acetyltransferase rhythm may be entrained by evening as well as by the morning light, while under very short photoperperiods the Rhythm may be synchronized by morning light only.
Abstract: Entrainment of a pacemaker driving the circadian rhythm in rat pineal N-acetyltransferase activity was studied under extremely long and short photoperiods. Adult male rats maintained under the light-dark regime (LD) 18:6 or under the regime LD 6:18 were exposed to a 1-min light pulse at different times at night, then they were released into darkness, and the next night phase-shifts of the evening N-acetyltransferase rise and of the morning N-acetyltransferase decline caused by light pulses were determined. The evening rise was phase-delayed by at most 0.5 h under LD 18:6, but by as much as 2.8 h under LD 6:18. The morning decline was phase-advanced by at most 1.9 h under LD 18:6, but by as much as 3.5 h under LD 6:18. Hence, the magnitude of phase-shifts and consequently patterns of phase-response curves, which show possibilities of discrete entrainment, depend on the photoperiods under which animals are maintained. A 1-min light pulse applied within 1 h before the end of the dark period phase-advanced the morning N-acetyltransferase decline under LD 18:6 as well as under LD 6:18, while a pulse applied within 1 h after the beginning of the dark period phase-delayed the evening N-acetyltransferase rise only in rats maintained under LD 18:6, but not in those kept under LD 6:18. It seems that under very long photoperiods, the N-acetyltransferase rhythm may be entrained by evening as well as by the morning light, while under very short photoperiods the rhythm may be synchronized by morning light only.
42 citations
TL;DR: The data suggest that growth of the winter pelage of mink is strongly associated with declining prolactin levels, and it appears that part of the photoperiodic‐induced effects on furrowth of the mink are mediated through melatonin and its effects on prolactIn synthesis and/or secretion.
Abstract: An experiment was conducted to determine the effects of a reduced daily photoperiod and exogenous melatonin on serum prolactin levels of mink during the autumn molt and growth of the winter pelage. During the last week of June, adult standard dark female mink (Mustela vision) were exposed to natural changes in daylength (controls), a reduced photoperiod of 6 h light: 18 h dark (6L:18D) or exposure to natural changes in daylength and treated with melatonin (10 mg) in a Silastic implant inserted subcutaneously over the scapular area. Beginning July 2, and continuing through October 22, blood samples were collected at nine biweekly intervals, and serum prolactin concentrations were quantified by a heterologous double antibody radioimmunoassay. Both reduced photoperiod and exogenous melatonin caused serum prolactin levels to decline rapidly after mid-July, resulting in concentrations that were significantly lower than those of controls 6 to 8 wk earlier. These data suggest that growth of the winter pelage of mink is strongly associated with declining prolactin levels. It appears that part of the photoperiodic-induced effects on fur growth of the mink are mediated through melatonin and its effects on prolactin synthesis and/or secretion.
39 citations
TL;DR: The results suggest that alloxan‐induced diabetics may decrease pineal melatonin synthesis in rats by reducing the activity of hydroxyindole‐O‐methyltransferase, resulting in a decrease in pinealmelatonin secretion.
Abstract: Effects of alloxan treatment on the levels of pineal melatonin, pineal N-acetylserotonin, and serum melatonin were investigated. Male rats were housed under a photoperiod of 12 h light: 12 h darkness and a temperature of 23 +/- 3 degrees C. Three weeks after alloxan (170 mg/kg) or carrier injection (s.c.), the animals were killed at mid-light (1200 h) and mid-dark (2400 h). Pineal and serum indoles were extracted and quantified by radioimmunoassays. It was found that pineal levels of N-acetylserotonin in the diabetic rats were significantly higher (P less than 0.05) than those of the controls. Conversely, pineal and serum levels of melatonin in the control rats were significantly higher (P less than 0.05) than those of the alloxan-induced diabetics. Our results suggest that alloxan-induced diabetes may decrease pineal melatonin synthesis in rats by reducing the activity of hydroxyindole-O-methyltransferase, resulting in a decrease in pineal melatonin secretion.
35 citations
TL;DR: Isoproterenol did retard the drop in NAT and melatonin after lights‐on at night, indicating that β‐receptors are involved in maintaining elevated melatonin levels.
Abstract: Thus far, all attempts to stimulate melatonin synthesis by beta-adrenergic receptor agonists in the Syrian hamster pineal gland have failed. Neither a wide range of dosages of isoproterenol (0.5 mg/kg to 24 mg/kg), nor prolonged treatment with norepinephrine, the natural neurotransmitter, increased N-acetyltransferase (NAT) activity or melatonin production. In the present study, the administration of isoproterenol at night was likewise ineffective in advancing or enhancing the normal nightly melatonin peak. Also, we did not find a delayed effect 7 or 8 h after the administration of the drug. Furthermore, we tested the idea of coneurotransmitters such as octopamine or dopamine being possibly necessary for stimulation, but could not find any effect of these substances on melatonin synthesis. In addition, a parasympatholytic agent, atropine, did not increase the responsiveness to sympathomimetic agents. Administration of a phosphodiesterase inhibitor was also ineffective in stimulating NAT activity. On the other hand, isoproterenol did retard the drop in NAT and melatonin after lights-on at night, indicating that beta-receptors are involved in maintaining elevated melatonin levels.
33 citations
TL;DR: Djungarian hamsters kept in long photoperiod were injected daily with 25 μg of melatonin and changed from summer to winter status with regard to all functions investigated responding simultaneously; i.
Abstract: Djungarian hamsters kept in long photoperiod (16:8 L:D) were injected daily at 0800, 1200, or 1600 with 25 micrograms of melatonin. During 90 days of treatment, body weight and fur coloration were checked at weekly intervals, and at the end of the treatment the reproductive status of the hamsters and their thermoregulatory properties (could limit, maximum thermoregulatory heat production, nonshivering thermogenesis, cytochrome oxidase activity in brown adipose tissue) were measured. Hamsters injected at 1600 changed from summer to winter status with regard to all functions investigated responding simultaneously; i.e., their body weights decreased, their fur became white, their gonads regressed, and their thermoregulatory properties improved. All these changes were identical to the effects of short photoperiod (8:16 L:D) exposure. Injections of melatonin at 0800 and 1200 were ineffective for reproductive functions, but the injection of melatonin at 0800 caused slight improvements of thermogenesis. The response to melatonin injected at 1600 could be suppressed by an additional injection of melatonin at 0800 (75 micrograms). Pinealectomized or ganglionectomized hamsters kept in long photoperiod did not respond to daily injections of melatonin at 1600 for the first 60 days of treatment, but during a prolonged treatment their sensitivity to melatonin was restored. Similarly, pinealectomized or ganglionectomized hamsters failed to respond to short photoperiod for about 40 days, but during prolonged exposure their sensitivity to short photoperiod was restored.
TL;DR: It is concluded that the photoperiodic information is translated into both nervous and indolic signals in cone‐like photoreceptor cells and into indolic messages in modified photorecept cells of the pineal parenchyma.
Abstract: Thin layer chromatography analysis of [3H]serotonin and [3H]melatonin metabolites synthetized in vitro by the pineal organ of the pike was performed. After a 10-min pulse, [3H]serotonin was mainly converted into [3H]-5-hydroxyindoleacetic acid (37%), [3H]-5-hydroxytryptophan and [3H]-5-methoxytryptophan (12 to 14%), and [3H]-5-hydroxytryptophol and [3H]-5-methoxytryptophol (3.5 and 9%) at the onset of darkness. When the pulse was followed by postincubations (in a cold medium) of increasing duration (15, 30, and 60 min), it appeared that 1) the amount of [3H]-5-hydroxyindoleacetic acid decreased, 2) that of [3H]-5-hydroxytryptophol decreased faster than that of [3H]-5-methoxytryptophol, and 3) the amounts of [3H]-5-hydroxy- and [3H]-5-methoxytryptophan increased. [3H]-N-acetylserotonin, [3H]melatonin, and [3H]-5-methoxytryptamine were found in very low amounts.
At the beginning of the photophase or at the onset of darkness, the uptake and metabolism of [3H]melatonin (after a 10-min pulse followed by a 10-min incubation in cold medium) resulted mainly in the formation of [3H]-5-methoxytryptophol (23 to 43%) and of [3H]-5-methoxytryptamine (6 to 12%).
These results show that the pike pineal organ can synthesize all indoles that are known in the pineal gland of higher vertebrates. Usual, but also unusual, pathways of the indole metabolism were found that will need further clarification. Among these are the possible carboxylation of serotonin and deacetylation of melatonin (leading to the synthesis of 5-methoxytryptophol). Altogether, the results obtained suggest that the indole metabolism might be more complex than what has already been described in vertebrates.
TL;DR: Melatonin is not a marker for general sympathetic activity, even following severe burn injury, and appears partitioned, with that controlling melatonin (nocturnal surge) regulated independently.
Abstract: Burn injury in humans or rats is a model of marked elevation of general sympathetic activity for weeks, manifested in part by increased heart rate, metabolic rate, core temperature, and plasma and urinary catecholamines. Plasma melatonin was sampled at 2-h intervals for 24 h in 9 control subjects and 11 patients with severe burn injury. Daytime melatonin was not different between the groups, but nighttime values were significantly lower in the burn patients. A nocturnal surge was still significant in the patients. Resting heart rate and rectal temperature were elevated in the burn patients. In male Spraguc-Dawley rats, pineal melatonin content did not differ between controls and those with an experimental burn at 4 h into the light phase nor during the nocturnal surge. Male Syrian hamsters with burns had lower daytime pineal melatonin content than did controls, but the nocturnal surge in pineal melatonin was not significantly different between groups, nor was daytime morning serum melatonin. Sympathetic activity appears partitioned, with that controlling melatonin (nocturnal surge) regulated independently. In agreement with our previous findings in other models, melatonin is not a marker for general sympathetic activity, even following severe burn injury.
TL;DR: The exocytosis number in A cells changes in relation to time of day, rising in early dark phase, and its rise following pinealectomy can be seen only in PF membranes.
Abstract: This research analyzed differences mainly in the incidence of exocytotic figures in adrenaline cells (A-cells) in pinealectomized (PX), sham-operated (SPX), and non-operated (NO) adult male golden hamsters, with the aim of determining whether these parameters change with the time of day and following pinealectomy, and whether intracellular regional differences exist in such changes. Animals acclimated to a standardized light:dark (LD) 12:12 photoperiod were sacrificed at 11 h after the onset of light (L-11h) and 1 h after the onset of darkness (D-1h) (8 animals/group/time) at 28 days postoperation. The adrenal medullas were examined and analyzed morphometrically by electron microscopy. The number of exocytoses per unit length (NEL) and the exocytosis index (a rough index of the number of exocytoses per cell) were measured in PF (perivascular-space-facing) and non-PF plasma membranes. NEL increased from L-11h (NO: 0.040 +/- 0.010, mean +/- SE) to D-1h (0.078 +/- 0.012) in all three experimental groups (ANOVA: P less than 0.005), showing over fourfold higher levels in PF than in non-PF membranes. NEL in PF membranes in PX animals showed higher levels than those in NO and SPX animals (P less than 0.025), but in non-PF membranes, no differences owing to time of day or surgery were seen. Exocytosis indices were (1) higher at D-1h than at L-11h in all three experimental groups (P less than 0.005), (2) similar in PF and non-PF membranes in control groups, and (3) higher in PF membranes in the PX group than in either non-PF membranes or PF membranes in control groups. In conclusion, the exocytosis number in A cells changes in relation to time of day, rising in early dark phase, and its rise following pinealectomy can be seen only in PF membranes.
TL;DR: The pyroantimonate technique was employed to demonstrate fine localization of Ca2+ in the superficial pineal gland of Meriones unguiculatus and obtained reaction product using an energy‐dispersive x‐ray microanalysis.
Abstract: In order to demonstrate fine localization of Ca2+ in the superficial pineal gland of Meriones unguiculatus, the pyroantimonate technique was employed. Control experiments were performed with EGTA and analysis of obtained reaction product using an energy-dispersive x-ray microanalysis.
Precipitates of calcium antimonate were formed almost exclusively in swollen clear pinealocytes, in and along their cell membranes, over their nuclei, in mitochondria, the Golgi apparatus, endoplasmic and integrade reticulums. acervuli, in vesicles surrounding synaptic bars, cytoplasmic matrix, and flocculent extracellular material. It has been concluded that the swollen pinealocytes represent a degenerative cell form probably occurring by impairment of plasmalemmal Ca2+-ATPase's ability to eliminate Ca2+ ion from the cell, with consecutive increase of calcium in the cytoplasmic matrix, followed by increase of intramitochondrial Ca2+ concentration, gradual arrest of mitochondrial function, depolymerization of cytoskeletal microtubuli, loss of the cell form, and cell death. Decrease of function of pinealocyte plasmalemma seems to be related to aging.
TL;DR: This work compared, in 28‐day‐old male rats, the effects of olfactory bulb deafferentation (peripheral anosmia) with those induced by either ofactory bulbectomy or blocking the AOS, alone or associated with blindness.
Abstract: Olfactory bulbectomy is known to potentiate the antigonadal effects of light deprivation. However, the physiological interpretation of the effects of bulbar ablation is complex, since it simultaneously implies sequelae like: a) the loss of olfactory sensitivity (anosmia), b) the suppression of the accessory olfactory system (AOS), and c) the suppression of nonsensorial functions of the bulbs. To study the participation of these three mechanisms in the effects of bulbectomy + light deprivation, we compared, in 28-day-old male rats, the effects of olfactory bulb deafferentation (peripheral anosmia) with those induced by either olfactory bulbectomy or blocking the AOS, alone or associated with blindness. As compared to the intact or blinded animals, both blinded deafferented (EA) and blinded bulbectomized (EB) rats showed various reductions in weights of body, testes, accessory sexual glands, and prostates; serum testosterone levels were also depressed. Testes of EA rats showed various degrees of alterations in spermatogenesis. The only difference between EA and EB groups was in the pituitary weight, significantly lower in EA rats.
TL;DR: N‐Acetyltransferase activity at night and following isoproterenol treatment in intact animals was higher in rats pretreated with magnesium than in controls, suggesting that magnesium acts primarily on the pineal gland as opposed to some other peripheral or central site.
Abstract: N-Acetyltransferase (NAT) activity at night and following isoproterenol treatment in intact animals was higher in rats pretreated with magnesium than in controls. This effect was probably due to enhancement of agonist binding and/or adenylate cyclase activation caused by magnesium ions. A similar effect was observed in vitro, where magnesium increased norepinephrine-stimulated NAT activity in organ-cultured pineal glands, suggesting that magnesium acts primarily on the pineal gland as opposed to some other peripheral or central site. This enhancement of NAT activity by magnesium would presumably lead to increased melatonin production; and as melatonin has been shown to decrease serum magnesium levels, a negative feedback mechanism may exist.
TL;DR: This finding and the day‐night differences in the gonadal response indicate that stress interferes with the metabolic cyclicity of the pineal gland, however, it remains indiscernible whether the Pineal stress reaction signals a general activation of the gland or a change in it's temporal activity patterns.
Abstract: Stress responses were investigated in 5-month-old male gerbils Breeders having no pubescent litters served as controls The first experimental group never left their parents' cage and were thereby fought by higher-ranking males; the second and third groups were stressed for a week by four daily 1-minute encounters with trained fighters, the second group during daytime, the third during the dark period The first and second groups developed signs of gonadal regression, the third did not The adrenals of the first group weighed the same as those of controls; the adrenals of both other groups were increased in weight In the adrenal medulla of all experimental groups, a large number of cells were densely packed with noradrenaline-containing vesicles In each experimental group the pineal changes included a remarkable decrease in nuclear size of pinealocytes, an increased number of colloidal cysts, and a reduction of that portion of the plasmalemma that is lined by subsurface cisterns All these changes are interpreted in terms of pineal activation, as are the increased number of membrane whirls found in the first group The third group exhibited an additional decrease in the size of mitochondria and in the number of "synaptic" structures This finding and the day-night differences in the gonadal response indicate that stress interferes with the metabolic cyclicity of the pineal gland However, it remains indiscernible whether the pineal stress reaction signals a general activation of the gland or a change in it's temporal activity patterns
TL;DR: The role of the pineal in regulating the oncogenic processes was explored in Sprague‐Dawley female rats by comparing incidence and growth of mammary tumors in animals subjected to superior cervical ganglionectomy with that of intact rats treated with 7–12‐ dimethylbenz(a)anthracene (DMBA).
Abstract: The role of the pineal in regulating the oncogenic processes was explored in Sprague-Dawley female rats by comparing incidence and growth of mammary tumors in animals subjected to superior cervical ganglionectomy (SCGx) or blinding and anosmia (BAs) with that of intact rats treated with 7–12- dimethylbenz(a)anthracene (DMBA). The surgery was performed at the age of 56 days, 1 day following the administration of the carcinogen. Growth of mammary tumors was studied, and 15 weeks later the rats were sacrificed by decapitation and the activity of the pineal hydroxyindole-O-methyltransferase (HIOMT) was determined. Carcinostatic effects of similar magnitude were present in both SCGx and BAs groups as evident from tendency toward reduced tumor incidence and decreased total tumor mass. Ganglionectomized rats developed significantly smaller numbers of tumors than intact control animals. A trend toward reduced tumor number and increased tumor regression was evident in the BAs group. Although there was no significant difference in tumor volumes among the groups, BAs animals showed a distinct trend toward smaller tumor volumes at the termination of the experiment. Despite similar carcinostatic tendencies, SCGx rats had significantly lower HIOMT activity than BAs animals. The possible existence of multiple carcinostatic mechanisms in BAs and SCGx rats is discussed.
TL;DR: Moonlight was unable to suppress pineal NAT activity and melatonin content even when the animals were exposed to the moonlight for 30 min, and the treatment of cotton rats with either norepinephrine or its agonist, isoproterenol, before their exposure to light at night retarded slightly the suppressive effect of light on the pineal constituents measured.
Abstract: In three separate experiments, the effect of acute exposure to either artificial or natural light during darkness of pineal N-acetyltransferase (NAT) activity and melatonin content was studied in the cotton rat (Sigmodon hispidus). The exposure of animals to an artificial-light irradiance of 160,000 microW/cm2 during darkness for either 1 s, 5 s, or 30 min was followed by a precipitous decline in pineal NAT activity and melatonin content when measured at either 15 or 30 min after light onset. When cotton rats were acutely exposed to light at night for 5 s, irradiances of either 3.2, 32, 320, and 3,200 did not suppress either pineal NAT or melatonin 30 min later; however, if the 5-s exposure had an irradiance of either 32,000 or 160,000 microW/cm2, the pineal enzyme activity and indole content were depressed. Moonlight, which had a maximal irradiance of 0.32 microW/cm2, was unable to suppress pineal NAT activity and melatonin content even when the animals were exposed to the moonlight for 30 min. The treatment of cotton rats with either norepinephrine or its agonist, isoproterenol, before their exposure to light at night retarded slightly the suppressive effect of light on the pineal constituents measured. Also, these drug treatments suppressed the pre-exposure levels of both NAT activity and melatonin content in the cotton rat pineal gland.
TL;DR: Data are consistent with the interpretation that immunohistochemically determined melatonin in unfixed pineal tissue is assessing binding of N‐acetylated indolealkylamines to pineal cell components.
Abstract: Melatonin binding in the pineal gland of albino rats is estimated using an immunohistochemical procedure. Binding is saturable, has relatively high affinity (Apparent KD= 2.7 nM), and competition studies indicate binding of indoleamines possessing an N-acetyl group on the terminus of the side chain (N-acetylserotonin and melatonin). These data are consistent with the interpretation that immunohistochemically determined melatonin in unfixed pineal tissue is assessing binding of N-acetylated indolealkylamines to pineal cell components.
In albino rats maintained on 12-hour light: 12-hour dark cycles, melatonin binding exhibits a diurnal rhythm with low levels of saturation (30%) early in the light and saturation by endogenous melatonin near the onset of darkness. An annual rhythm of melatonin binding was observed in albino rats with low levels during the summer and high levels during the winter. Other rats were maintained on 12-hour light: dark cycles and fed for 2 hours either early in the light period or early in the dark period. For both morning- and evening-fed animals, melatonin binding was high prior to feeding and dropped immediately after feeding. Changes in melatonin binding that occur in response to alterations of feeding and time of year suggest the possibility that this binding reflects a functional site for melatonin.
TL;DR: Rat pinealocytes were found to contain mitochondria in three configurational states and they were calculated during their maximum and minimum serotonin content under various conditions of lighting, indicating the existence of correlation between pinealocyte bioenergetics and melatonin biosynthesis and its lack in relation to serotonin.
Abstract: Rat pinealocytes were found to contain mitochondria in three configurational states and they were calculated during their maximum (11:00) and minimum (23:00) serotonin content under various conditions of lighting (LD 12:12 and D 24). Their proportions were found to change in the circadian rhythm. Analysis of these results indicated the existence of correlation between pinealocyte bioenergetics and melatonin biosynthesis and its lack in relation to serotonin. Cell groupings with mitochondria in the same configurational state were observed, which suggests the existence of functionally differentiated zones within the pineal gland. In this context, the biochemically demonstrated circadian rhythm in the pineal gland secretion results from the synchronization at the organ level arising from the resultant function of individual pinealocytes.
TL;DR: The suggestion is made that the pineal gland acts to monitor illuminance levels (below about 0.02 scotopic fc) as well as photic duration, and the latter appears to be an “all or none” effect, while the former seems to be graded.
Abstract: Three different light sources were used to determine the effects of spectral power distribution (SPD) and illuminance levels on growth and organ weights of male golden hamsters and rats. SPD had little effect on organ weights or measurements of either rats or hamsters. However, responses to illuminance levels were quite apparent, provided they were equalized for the scotopic eye sensitivity curve characteristic of nocturnal animals. Under seven illuminance levels from 0 to 3.9 scotopic fc, hamsters demonstrated graded responses in gonadal weights and presumed function from 0 to 0.02 scotopic fc. Above this level, photopic saturation was apparent. The neuroendocrine system of pinealectomized animals failed to show sensitivity to illuminance levels. The suggestion is made that the pineal gland acts to monitor illuminance levels (below about 0.02 scotopic fc) as well as photic duration. While the latter appears to be an "all or none" effect, the former appears to be graded.
TL;DR: Blind hamsters had no alteration of the dialyzable fraction of serum thyroxine (T4) but had depressed total and free T4 concentrations compared to controls and prevention of the effects of blinding by pinealectomy indicates pineal influence on circulatingfree T4 concentration.
Abstract: Blind hamsters had no alteration of the dialyzable fraction of serum thyroxine (T4) but had depressed total and free T4 concentrations compared to controls. Prevention of the effects of blinding by pinealectomy indicates pineal influence on circulating free T4 concentration. Parallel changes in free T4 and the free T4 index indicate adequacy of the index in representing pineal-induced changes in free T4.
TL;DR: Since olfactory bulb deafferentation potentiates the antigonadal effects of light deprivation, the pineal involvement in this action was studied and whether peripheral anosmia might increase the response to melatonin injections was studied.
Abstract: Since olfactory bulb deafferentation (peripheral anosmia) potentiates the antigonadal effects of light deprivation, we studied a) the pineal involvement in this action and b) whether peripheral anosmia might increase the response to melatonin injections.
Four-week-old male rats were used in two experimental series. The first included rats in which blindness + peripheral anosmia was associated with either pinealectomy or sham pinealectomy. In the second series, intact, olfactory bulb deafferented and bulbectomized rats received daily injections of either melatonin (50 μg) or the vehicle alone. In both experiments animals were killed at 10 weeks of age.
The reduction in the weight of accessory sexual glands and prostates, as well as in the serum testosterone levels, induced by blindness + peripheral anosmia was fully prevented by pinealectomy, whereas body and pituitary weight reduction induced by the dual sensory deprivation were only partially prevented. Melatonin produced no effects in intact animals whereas in rats with either peripheral anosmia or bulbectomy it reduced the weight of body, accessory sexual glands, and prostates. Serum testosterone levels were not modified in any case with melatonin treatment. From these results we concluded that the antigonadal effects of blindness + peripheral anosmia are pineal-dependent, that peripheral anosmia sensitizes the neuroendocrine reproductive axis to the antigonadal effects of exogenous melatonin, and that the reduction in the weight of testosterone-dependent organs induced by melatonin in bulbectomized or deafferented animals, together with the normal serum testosterone levels observed, suggests peripheral actions of melatonin of possible antiandrogenic nature.
TL;DR: The study indicates that the demethylation of melatonin is a specific metabolic pathway that does not apply to other methoxyindoles.
Abstract: Though melatonin is primarily metabolised to 6-hydroxy-melatonin, we have recently shown that it can also be demethylated to form N-acetyl-serotonin. The question therefore arises as to whether demethylation is a general metabolic pathway that can apply to other pineal methoxyindoles. To investigate this possibility we administered deuterated methoxy-tryptophol (dML) and deuterated methoxy-tryptamine (dMT) to rats and analysed the urine for the presence of deuterated methoxyindole acetic acid (dMIAA) and deuterated hydroxyindole acetic acid (dHIAA). The method of analysis was gas chromatography mass spectrometry (GCMS), where the relevant molecular ion and fragment ions were monitored. The results showed that the major metabolite in all cases was dMIAA. There was no evidence to suggest that the compounds had been demethylated to form dHIAA. The study therefore indicates that the demethylation of melatonin is a specific metabolic pathway that does not apply to other methoxyindoles.
TL;DR: Animals born in the dark possessed larger testes than those born in LD cycles and displayed less responsiveness to levels of illumination below those required to suppress pineal function, suggesting that the pineal gland may act indirectly as a photodosimeter at low illuminance levels.
Abstract: Four-week-old male hamsters, born and raised in total darkness or in LD 14: 10 (hr) were exposed to several low levels of illumination for 14 weeks. Analyses showed that testicular weights were significantly affected by both photic history and illuminance levels. Animals born in the dark possessed larger testes than those born in LD cycles and, further, displayed less responsiveness to levels of illumination below those required to suppress pineal function. While gonadal responses to photic duration may be said to be “all or none,” those resulting from insufficient illuminance levels are seemingly graded. Thus, the pineal gland may act indirectly as a photodosimeter at low illuminance levels.
TL;DR: The evidence suggests that differences occur in the rate‐limiting steps in the indolealkylamine biosynthesis in the three brain areas in the light and dark phases.
Abstract: The simultaneous effect of α-monofluoromethyldopa (MFMD) on the synthesis of rat brain indolealkylamines has been investigated both in the daytime and in the dark phase. The effect on serum melatonin concentration has also been determined in the dark period. MFMD inhibits 5-hydroxytryptophan decarboxylase in the pineal gland, hypothalamus, and the cerebral cortex. Simultaneous measurement of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) levels in the three brain areas revealed that MFMD caused (1) large increases in pineal 5-HTP concentrations and substantial decreases in pineal 5-HT and 5-HIAA both in the light and dark phases; (2) a significant decrease in daytime hypothalamic 5-HT content after 7-h pretreatment; and (3) a large increase in dark-phase cortical 5-HT concentration after 4-h pretreatment. Serum melatonin levels were also reduced by the action of MFMD in the dark period. The evidence suggests that differences occur in the rate-limiting steps in the indolealkylamine biosynthesis in the three brain areas.
TL;DR: Pineal N‐acetyltransferase activity (NAT) has a circadian rhythm with peak values in the dark time and lowvalues in the light time, measured in rats exposed to LD 14:10, to constant dark, and to acute lightdark treatments.
Abstract: Pineal N-acetyltransferase activity (NAT) has a circadian rhythm with peak values in the dark time and low values in the light time. NAT time profiles were measured in rats exposed to LD 14:10, to constant dark, and to acute (less than 48 hr) lightdark treatments.
In all experiments, imposition of light suppressed NAT. The phase of the dark time NAT cycle was altered 2 hr or less by the following treatments: 3 hr light in the early subjective night, 3 hr light in the late subjective night, 2 hr or 6 hr light in the early subjective day, 4 hr early lights-on, 1 day of constant dark, or 1 day of constant light. When light was extended 4 hr into the dark time, NAT rose at lights out but fell again as the time of “expected” dawn approached.
In contrast, the phase of the NAT cycle was shifted 12 hr (180°) within 72 hr by reversing the phase of the light-dark cycle. NAT did not rise in the first dark period (coincident with the time of the subjective light time). The amplitude of the first shifted cycle was less than four control NAT profiles measured in rats kept in the original (unshifted) light dark cycle.
TL;DR: Low concentrations of aracbidonate, oleate, or palmitate affected the cycle of NAT activity of cultured chick pineal glands in different ways and were altered by change of the lighting conditions of culture.
Abstract: Low concentrations of aracbidonate, oleate, or palmitate signficantly affected the cycle of NAT activity of cultured chick pineal glands in different ways. The effects observed were altered by change of the lighting conditions of culture. Effects of arachidonate were also shown to be altered by change of the serum component of the culture medium.
Effects of premature exposure to light of glands cultured under diurnal conditions of illumination were changed markedly by substitution of the serum component of the medium or a supplement of ionophore A23187 and less markedly by supplements of fatty acids.