Showing papers in "Journal of Pineal Research in 1986"
TL;DR: Melatonin production clearly declined with age but was not influenced by other demographic variables or by season of the year.
Abstract: The purpose of this study was to investigate the effects of time of year and demographic variables on the amplitude of melatonin production in normal human subjects. Melatonin production was estimated by measuring the overnight excretion of its major urinary metabolite, 6-hydroxymelatonin. Urine was collected on three consecutive nights in the summer from a sample of 60 normal subjects balanced for sex and age. The collections were repeated in a subgroup during the winter. Melatonin production clearly declined with age but was not influenced by other demographic variables or by season of the year.
393 citations
TL;DR: The results indicate that in humans the circadian organizatijon for serotonin already exists at birth, and the circadian melatonin rhythm develops after birth.
Abstract: The serum concentration of melatonin, serotonin, and N-acetylserotonin were measured by RIA procedures in 28 infants aged 1 week to 9 months. Blood specimens were obtained at 12:00 hr and 24:00 hr. A day-night difference in serum serotonin was present immediately after birth. A significant (P less than 0.001) decrease in serum serotonin concentrations at 12:00 hr and 24:00 hr was observed from the first month of age to the third to ninth month of age. A significant (P less than 0.05) difference in day-night N-acetylserotonin concentration is first seen at age 1-3 months. Serum melatonin concentrations, though detectable, did not show any day-night difference at birth. Melatonin concentrations progressively increased up to the third month of age, and a significant (P less than 0.01) day-night difference appeared thereafter. The results indicate that in humans the circadian organization for serotonin already exists at birth, and the circadian melatonin rhythm develops after birth.
95 citations
TL;DR: It is hypothesized that this hormone has physiological action within the gut, including motility, however, its action may not be directly on smooth muscle contraction but may be through an indirect action inhibiting the contractile response of serotonin, as suggested by other investigators.
Abstract: Segments from various locations of the small and large intestine of the rat were removed, bathed in Tyrode's solution and attached to a force displacement transducer. Melatonin, while not influencing the frequency of contraction, did reduce the force of spontaneous contractions of duodenal and colon segments of rat intestine by 92 and 52%, respectively compared to only 25 and 22% for the ileum and jejunum, respectively. Areas with greatest responsiveness to melatonin were those that previous studies have shown to contain the largest concentrations of endogenous melatonin. Cyclic guanosine monophosphate, when tested in similar preparations, did not produce an inhibitory response characteristic of melatonin. It is hypothesized, therefore, that this hormone has physiological action within the gut, including motility; however, its action may not be directly on smooth muscle contraction but may be through an indirect action inhibiting the contractile response of serotonin, as suggested by other investigators.
90 citations
TL;DR: Results support a link between pineal activity and brain BZP receptors in rats and support the idea that pineal removal blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon.
Abstract: In a previous work, pinealectomy was found to depress benzodiazepine (BZP) receptor binding in cerebral cortex membranes of rats killed at noon. In order to assess the effect of pineal removal on diurnal variations of BZP binding site concentration and affinity, groups of intact, pinealectomized, or sham-pinealectomized rats (subjected to surgery 2 wk earlier) were killed at six different time intervals during the 24-h cycle. BZP binding was assessed by Scatchard analysis of 3H-flunitrazepam high-affinity binding to cerebral cortex membranes. In intact and sham-pinealectomized rats, a maximum in BZP receptor concentration was found at midnight. Pinealectomy blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon. No changes in the affinity of the binding sites for the radioligand were detected as a function of time of day or following surgery. In a dose-response experiment for melatonin ability to restore the depressed BZP receptor concentration of cerebral cortex membranes of pinealectomized rats killed at noon, a minimal effective dose of 25 micrograms/kg body weight was obtained. These results further support a link between pineal activity and brain BZP receptors in rats.
86 citations
TL;DR: A dose‐dependent increase in tone and reduction in amplitude of contractions was observed after serotonin (5‐HT) was administered to isolated segments of rat ileum, incubated in Locke's solution at 38°C, and methysergide could not reduce the muscle tone and did not relieve spasm caused by 5‐HT, suggesting M is not acting as antagonist of 5‐ HT‐ stimulatory receptors but rather as agonist of 5-HT‐inhibiting neuronal receptors.
Abstract: A dose-dependent increase in tone and reduction in amplitude of contractions was observed after serotonin (5-HT) was administered to isolated segments of rat ileum, incubated in Locke's solution at 38°C. Melatonin (M) reduced the tone but not the amplitude or frequency of contractions. Addition of M (administered in doses 20 to 100 × higher than 5-HT) relieved the spasm induced by 5-HT. Furthermore, pretreatment with M significantly reduced the 5-HT effect. N-acetylserotonin (NAS) exhibited delayed but similar effects to M. Neither M nor NAS could prevent or relieve acetylcholine-induced contractions or influence relief of intestinal contractions by adrenaline. This indicates that 5-HT and M act via a different mechanism than that of adrenaline and acetycholine system. Serotonin muscle receptor blocker methysergide reduced 5-HT effect but was not able to abolish it completely. As methysergide could not reduce the muscle tone and did not relieve spasm caused by 5-HT, it is speculated that M is not acting as antagonist of 5-HT- stimulatory receptors but rather as agonist of 5-HT-inhibiting neuronal receptors.
80 citations
TL;DR: The data do not favor a direct relationship between melatonin secretion and the sleep‐waking cycle in humans and Chi‐square testing revealed that the nocturnal pattern of melatonin levels was not related to sleep stages.
Abstract: The concentration of melatonin was determined, using a sensitive and reliable radioimmunoassay, in plasma samples obtained at 20 min intervals during a 12 hr period (from 20.00 to 8.00) from six normal men. Polygraphic sleep recording was simultaneously performed. Each subject was studied twice at a 1 week interval. For each session, the plasma melatonin profile showed an episodic secretion: a mean frequency of 4.5 peaks and 4.0 troughs per night in the first study and a mean frequency of 4.0 peaks and 3.5 troughs in the second study. The two nocturnal melatonin profiles obtained from each subject were very similar. However, considerable interindividual variation was found (areas under the curve [AUC] from 15.3 to 125 pg X hr/ml). No relationship could be obtained between AUC and body weight. Apparent melatonin half-life calculated from the semilogarithmic plots of the melatonin pattern was 57 +/- 34 min. Chi-square testing revealed that the nocturnal pattern of melatonin levels was not related to sleep stages. Our data do not favor a direct relationship between melatonin secretion and the sleep-waking cycle in humans.
70 citations
TL;DR: Intracranial injections of 10 μg melatonin, with or without 4 μg naloxone, result in reduced aggressive responsiveness by the cichlid fish Aequidens pulcher to a mirror presented 20 min later, which suggests that the behavioral action of 5HT‐CS may be mediated by its conversion to melatonin.
Abstract: Intracranial injections of 10 micrograms melatonin, with or without 4 micrograms naloxone, result in reduced aggressive responsiveness by the cichlid fish Aequidens pulcher to a mirror presented 20 min later. Naloxone, when administered on its own, had no behavioral effect. Intracranial injections of 25 micrograms serotonin-creatinine sulphate complex (5HT-CS) also reduced aggression. 5HT-CS's action was abolished if the injection included 10 micrograms S-adenosyl homocysteine (SAH), which inhibits the conversion of serotonin to melatonin. This suggests that the behavioral action of 5HT-CS may be mediated by its conversion to melatonin. There is inconclusive evidence to suggest that 37.5 micrograms 5HT-CS, administered in conjunction with 10 micrograms SAH, may reduce aggressiveness; injection of 50 micrograms 5HT-CS, with or without 10 micrograms SAH, induced a pronounced escape behavior which precluded any measurement of aggressiveness in the fish.
63 citations
TL;DR: The existence of a phase‐response curve (PRC) for melatonin suggests that the daily endogenous rhythm of melatonin may be involved in phasing, or entraining, the circadian system of lizards.
Abstract: Single biweekly injections of melatonin were administered to lizards (Sceloporus occidentalis) free-running (exhibiting their endogenous circadian activity rhythm) in constant dim illumination. The injections caused phase shifts in the activity rhythm whose magnitude and direction were a function of the time of the melatonin injections, relative to activity onsets. Plotting the direction and amount of phase shift versus the time (phase) at which the injection was given generates a phase-response curve (PRC). The PRC shows that injections administered between midsubjective day and early subjective night (6–15 hr after activity onset) elicit phase advances in the activity rhythm, whereas injections given at other phases of the activity cycle induce phase delays. The existence of a PRC for melatonin suggests that the daily endogenous rhythm of melatonin (i. e., of pineal origin) may be involved in phasing, or entraining, the circadian system of lizards. The shape of the PRC also allows predictions as to the effects of continuous exogenous melatonin administration on the period of free-running activity rhythms as well as on the mechanism of entrainment of activity rhythms to daily melatonin injections.
54 citations
TL;DR: It is concluded that pineal hormones have sleep‐promoting effects, but that their correlation with the lightdark cycle does not imply that they are causal factors in generating diurnal rhythms of sleep and wakefulness.
Abstract: Melatonin and 5-methoxytryptamine were administered continuously over a period of 1-3 months to adult male rats by means of subcutaneously implanted silastic capsules containing one or the other of these pineal hormones. Polygraphic recordings during several weeks following hormonal application showed an increase in the amount of time spent in both quiet and rapid eye movement sleep, during the light as well as the dark period; however, diurnal sleep-wake rhythmicity was not affected by either treatment. We conclude that pineal hormones have sleep-promoting effects, but that their correlation with the light-dark cycle does not imply that they are causal factors in generating diurnal rhythms of sleep and wakefulness.
48 citations
TL;DR: Melatonin treatment had no significant effect on seasonal variation of T3, or T4, and no statistical differences in levels of alkaline phosphatase were seen between groups, although concentrations in experimental bucks sharply dropped to basal levels two months ahead of controls.
Abstract: Five milligrams of melatonin (M) per day was administered orally to four male white-tailed deer on a schedule that mimicked first decreasing and then increasing lengths of natural photoperiod The following seasonal phenotypic and hormonal responses were observed: 1) Pelage exchange, antler mineralization, velvet shedding, and rutting behavior of experimental animals were advanced by 50–55 days 2) Prolactin (PRL) levels exhibited a bimodal curve with peaks in May and August, as compared to a monomodal curve of controls (peak in June) 3) Peak FSH levels of M-fed deer were advanced 2 months as compared to controls (June vs August) 4) LH concentrations of both groups reached maxima in July; however, in the experimental group, LH levels declined much faster than in controls and then rose again in October-November 5) Testosterone (T) concentrations of M-fed bucks were elevated 2 months ahead of controls 6) Melatonin treatment had no significant effect on seasonal variation of T3, or T4 7) No seasonal rhythm of cortisol was seen in either group and no detectable effect of M was evident 8) No statistical differences in levels of alkaline phosphatase were seen between groups, although concentrations in experimental bucks sharply dropped to basal levels two months ahead of controls
46 citations
TL;DR: The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy and pinealectomy in male Syrian hamsters, which appears to depend on the pineal gland and its sympathetic innervation.
Abstract: The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy in male Syrian hamsters. Ganglionectomy and pinealectomy each prevented the nocturnal rise of serum melatonin concentration seen in control animals. The normal nocturnal surge of circulating melatonin in this species appears to depend on the pineal gland and its sympathetic innervation.
TL;DR: There was no synchronous periodic kemp activity: some follicles remained active at all times, and the seasonal pattern of plasma prolactin levels disappeared, but the relationship between the kemp follicle cycle and the pattern of Plasma Prolactin concentrations and its control by the pineal gland are discussed.
Abstract: Twelve adult Limousine rams (five pinealectomized, four sham operated, and three control) were housed under an artificial lighting regime of alternating periods of long (16L:8D) and short (8L:16D) days for 18 months, and long-term variations in kemp follicle growth were recorded along with measurements of the plasma prolactin concentrations. In control and sham-operated rams, both parameters varied in relation to imposed lighting regime. Moult and growth of the kemp follicles occurred during each short-day period at a time when the concentrations of prolactin were low and vice versa. Variations in the pinealectomized rams were different from those in the control or sham-operated ones. There was no synchronous periodic kemp activity: some follicles remained active at all times, and the seasonal pattern of plasma prolactin levels disappeared. The relationship between the kemp follicle cycle and the pattern of plasma prolactin concentrations and its control by the pineal gland are discussed.
TL;DR: Methoxytryptamine and serotonin inhibited hormone‐induced lipolysis in a dosedependent manner and exhibited the highest antilipolytic activity in isolated rat, rabbit, and hamster adipocytes, however, their antilipsic activity could not be overcome by increasing the dose of the lipolytic hormone.
Abstract: The effects of arginine vasotocin and the pineal indoles melatonin, serotonin, N-acetylserotonin, hydroxytryptophol, methoxytryptophol, hydroxyindoleacetic acid, methoxyindoleacetic acid, and methoxytryptamine on lipolysis and lipogenesis in isolated adipocytes were studied. Basal lipolysis was inhibited by all the indoles tested at a dose of 1 mumole except hydroxytryptophol. Methoxytryptamine and serotonin inhibited hormone-induced lipolysis in a dose-dependent manner and exhibited the highest antilipolytic activity in isolated rat, rabbit, and hamster adipocytes. However, their antilipolytic activity could not be overcome by increasing the dose of the lipolytic hormone. Dibutyryl cyclic AMP-induced lipolysis was also inhibited. All the pineal indoles tested were capable of suppressing basal and insulin-stimulated lipogenesis in the dose range 0.33-3 nmole. At lower doses there was no effect. Arginine vasotocin at a dose of 25 nmole significantly augmented basal lipogenesis.
TL;DR: Observations suggest that melatonin, in addition to mediating short photoperiod‐induced gonadal regression in the Syrian hamster, also brings about thermoregulatory adjustments necessary for hibernation.
Abstract: This study investigated whether short photoperiod or melatonin-treatment could alter the thermogenic capacity of Syrian hamsters. Exposure of hamsters to short photoperiod and to exogenous melatonin treatment induced gonadal regression and hypertrophy of brown adipose tissue (BAT). Short photoperiod and melatonin-induced BAT hypertrophy was not accompanied by any change in noradrenaline (NA) turnover in this tissue. The concentration of NA was significantly decreased in hypertrophied BAT, indicating that sympathetic innervation in BAT did not effect its hypertrophy. No improvement in nonshivering thermogenic capacity was noticed in hamsters with increased BAT mass. However, capability for shivering thermogenesis seemed to be enhanced in melatonin-treated hamsters. These observations suggest that melatonin, in addition to mediating short photoperiod-induced gonadal regression in the Syrian hamster, also brings about thermoregulatory adjustments necessary for hibernation.
TL;DR: Diurnal variations in plasma melatonin concentrations have been measured in intact and ganglionectomized females maintained under long or short days after mating to understand if the diurnal variation of melatonin secretion is part of the mechanism by which the mink measure day length.
Abstract: Removal of the superior cervical ganglia suppresses the inhibitory role of short days in prolactin secretion and luteal activity in pregnant or pseudopregnant mink. Alternatively, timed injections of melatonin replicate the inhibitory role of short days in females maintained under long days. To understand if the diurnal variation of melatonin secretion is part of the mechanism by which the mink measure day length, diurnal variations in plasma melatonin concentrations have been measured in intact and ganglionectomized females maintained under long or short days after mating. Melatonin was measured by radioimmunoassay according to Brun et al. [Adv. Biosci. 53:41-45]. In intact females, plasma concentrations ranged from nondetectable levels to 40 pg/ml during the day, increased shortly after the onset of the dark phase, and reached peak values during the middle of the night. The duration of the elevated levels was roughly proportional to the length of the night. No diurnal variations could be detected in ganglionectomized females; melatonin levels never exceeded the day values observed in intact females.
TL;DR: The presence of a quisqualate‐type, Cl−/Ca2+‐dependent glutamate binding site in the pineal organ is suggested, and a possible neuroexcitatory role for glutamic acid, aspartic acid, and certain sulfur‐containing amino acids is also implied.
Abstract: The presence of a high concentration of glutamic acid, a transmitter shown to have excitatory action in the pineal organ, prompted us to search for and to characterize glutamate receptor site in the bovine pineal organ. By using 10 nM- 100 microM of labeled and unlabeled L-glutamate and by employing the LIGAND computer program, we found a glutamate binding site with a dissociation equilibrium constant (KD) of 0.534 microM and a receptor density (Bmax) of 4.84 pmol/mg protein. This pH- and temperature-dependent binding site showed stereospecificity, was activated by Ca2+, and displayed affinity for both glutamate agonists and antagonists. The IC50 values for L-glutamate, L-aspartate, L-cysteate, L-cysteine sulfinate, quisqualate, and (+/-) ibotenate were 0.5, 2, 12, 16, 25, and 30 microM, respectively, whereas those for D-aspartate, L-alpha-aminoadipate, L-homocysteate, and DL(+/-) 2-amino-4-phosphonobutyrate were greater than 100 microM. Kainate, N-methyl-D-aspartate, and L-glutamic acid diethyl ester were inactive. Based on these results, the presence of a quisqualate-type, Cl-/Ca2+-dependent glutamate binding site in the pineal organ is suggested, and a possible neuroexcitatory role for glutamic acid, aspartic acid, and certain sulfur-containing amino acids is also implied. The precise nature of this excitatory effect in modulating the function(s) of the pineal organ and the synthesis of its hormone(s) remains to be elucidated.
TL;DR: Melatonin (10μg and/or 100μg injection) decreased significantly the mean mitotic activity rate (MMAR) of TFC in both male and female mice and totally suppressed the stimulatory effect of TSH on the MMAR in both sexes of mice.
Abstract: The aim of the present study has been to examine the effect of melatonin, administered to mice as daily subcutaneous injections for a total of 10 days, on the mitotic activity of thyroid follicular cells (TFC). The colchicine metaphase-arrest technique was employed in the experiment. We found that melatonin (10 micrograms and/or 100 micrograms injection) decreased significantly the mean mitotic activity rate (MMAR) of TFC in both male and female mice. Moreover, melatonin totally suppressed the stimulatory effect of TSH on the MMAR of TFC in both sexes of mice. Furthermore, the effect of melatonin (5 X 10(-7) M) on the proliferation of TFC in the organ-cultured rat and mouse thyroid explants was investigated. It was found that melatonin almost totally suppressed the MMAR of TFC in organ culture. Moreover, melatonin blocked the stimulatory effect of TSH on the MMAR of TFC in both rat and mouse thyroid explants. N-acetylserotonin (NAc-5HT, 10(-6) M) also decreased the MMAR of cultured thyroid explants, but its effect was less expressed when compared to melatonin inhibition. The present data indicate that melatonin can exert its inhibitory effect on the proliferation of TFC directly at the thyroid level, since this pineal indoleamine has been shown to suppress not only basal but also TSH-stimulated mitotic activity. The results are in agreement with the hypothesis of a pineal-thyroid negative feedback, assuming the direct inhibitory effect of melatonin on the thyroid growth.
TL;DR: NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster, and might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.
Abstract: Norepinephrine (NE, 10(-6) M) stimulated melatonin accumulation in the incubation medium of rat (but not Syrian hamster) pineals taken at the end of the light phase. However, NE elevated melatonin accumulation in the medium of pineals taken after 20 min of light exposure of animals of either species at 6 h into the 10-h dark phase. A dose response to 10(-7)-10(-5) M NE was observed in both the medium and pineals upon incubation of pineals taken from rats at 4 h into the light phase and from hamsters after 20 min light exposure at 6 h into the dark phase. Approximately 95% of the melatonin present was in the medium. The incubation time was 4 h in all cases. Subcutaneous injection of 1 microgram/g NE (either at the end of the light phase or after 30 min of light at 6 h into the dark phase) did not stimulate in vivo Syrian hamster pineal melatonin content determined 1 or 2 h after injection, whether the hamsters were placed in light or darkness after the injection. However, after 30 min of light beginning at 6 h into dark, injection of 5 micrograms/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 microgram/g NE, observed at 1 and 2 h in light after injection. A small effect of DMI alone was seen. DMI also potentiated the effect of NE (each 10(-6) M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night. No significant stimulatory effect of NE and/or DMI was seen in vivo or in vitro near the middle of the light phase. Measurement of melatonin in the incubation medium is a useful method for studying pineal function. The Syrian hamster pineal has rhythm of sensitivity to NE (sensitivity evident at night) and even at night is protected by neuronal uptake from circulating NE-induced stimulation of melatonin production. NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster. The sensitivity rhythm and uptake protection might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.
TL;DR: The circadian plasma melatonin profile of a marsupial, the tammar, was determined at various stages of the annual reproductive cycle, andMelatonin concentrations were elevated during the dark phase of each photoperiod, and there were significant changes between the profiles in each season.
Abstract: The circadian plasma melatonin profile of a marsupial, the tammar, was determined at various stages of the annual reproductive cycle. At 6-14 days after each of the solstices and equinoxes, six females were exposed to a photoperiod equivalent to the natural day length at these times. Serial blood samples were taken 8 days later at 2-4-hourly intervals, and plasma melatonin concentrations were measured by radioimmunoassay. Melatonin concentrations were elevated during the dark phase of each photoperiod, and there were significant changes between the profiles in each season. The amplitude of the nocturnal rise was significantly higher (P less than 0.05) during the breeding season after the summer solstice (peak 259.5 +/- 26.8 pg/ml, mean +/- SEM) and autumnal equinox (287 +/- 53.2 pg/ml) compared to those during the nonbreeding season after the winter solstice (111.5 +/- 10.5 pg/ml) and vernal equinox (154.5 +/- 10.4 pg/ml). The duration of the nocturnal rise was significantly correlated (r=0.996, P less than 0.01) with the length of the dark phase and so was shortest after the summer solstice and longest after the winter solstice. Either of these changes in amplitude or duration might provide the photoperiodic information that regulates the annual reproductive cycle of the tammar.
TL;DR: Melatonin injected in a single intraperitoneal dose of 100 μg/100 g b.
Abstract: Melatonin injected in a single intraperitoneal dose of 100 micrograms/100 g b.w. to euhydrated rats resulted in a decrease of neurohypophysial oxytocin content but the hypothalamic oxytocin storage as well as the hypothalamo-neurohypophysial storage of vasopressin were not changed. Following 8 d of once-daily melatonin treatment the hypothalamic and neurohypophysial oxytocin and vasopressin content was decreased. It might be therefore suggested that melatonin increases the release of neurohypophysial hormones and/or decreases their synthesis. Melatonin did not significantly modify the neurohypophysial vasopressin depletion rate in animals deprived of water up to 8 days. No consistent effects of melatonin on the decrease of hypothalamo-neurohypophysial content of oxytocin were noted under conditions of dehydration and simultaneous administration of melatonin up to 8 d.
TL;DR: The spontaneous activity of 117 pineal units was recorded in urethane‐anesthetized rats and microiontophoretic application of norepinephrine induced changes of firing rates in 61% of the Pineal units tested.
Abstract: The spontaneous activity of 117 pineal units was recorded in urethane-anesthetized rats. The pineal units exhibited a wide range of firing rates of which 50% were on average slower than 14 spikes per second. Superior cervical ganglion (SCG) stimulation was studied in 76 pineal units; this stimulation caused excitation in 55% of the units. Microiontophoretic application of norepinephrine (NE) induced changes of firing rates in 61% of the pineal units tested. Two patterns of activity following NE microiontophoresis was observed: increase in firing rate (64%) and decrease in firing rate (36%). NE-induced excitation was observed only in those units excited by SCG stimulation. When NE and SCG stimulation were applied together, partial summation of the excitation induced by each one alone was observed. None of the units in which NE depressed the firing rate responded to SCG stimulation. Local application of propranolol blocked the excitation initiated by SCG stimulation as well as the excitation and the depression induced by NE microiontophoresis.
TL;DR: The results indicate that the information about external light‐dark cycles is converted by the pineal gland into the endocrine signal as a daily pattern of melatonin secretion, which eventually regulates prolactin secretion from the pituitary gland of the goat.
Abstract: The effects of timed melatonin infusion on prolactin secretion were examined in the pineal denervated goat. Ovariectomized Shiba goats (n = 5) were subjected to bilateral superior cervical ganglionectomy (SCGX); this procedure resulted in complete abolition of endogenous melatonin release during the dark phase. SCGX goats failed to coordinate their prolactin secretion with the prevailing photoperiod. Melatonin was infused (20 micrograms/h, s.c.) daily into these goats either for 8 h (the long-day-type infusion) or for 16 h (the short-day-type infusion) to mimic the nocturnal profile of plasma melatonin under long days or short days, respectively. The long-day-type melatonin infusion for 9 days, in comparison with control saline infusion, accelerated prolactin secretion, inducing a nocturnal rise in plasma prolactin; this was comparable to that seen in the pineal intact goats under long photoperiods. On the other hand, the short-day-type melatonin infusion suppressed prolactin secretion throughout the day as the short-day treatment did in intact goats. The prevailing photoperiod appeared to have no distinct effect on these prolactin responses to exogenous melatonin, which were indistinguishable under 16L8D and 8L16D conditions. The results indicate that the information about external light-dark cycles is converted by the pineal gland into the endocrine signal as a daily pattern of melatonin secretion, which eventually regulates prolactin secretion from the pituitary gland of the goat.
TL;DR: Daily excretion values for 6‐oxymelatonin in healthy subjects correlate with both FTS titers and cortisol content, while the latter two correlate with each other (P < 0.05).
Abstract: Results are given of daily excretion levels of 6-oxymelatonin, thymic serum factor (FTS), and cortisol in the blood of 140 healthy subjects and 90 patients with skin melanoma, ranging from 20 to 49 years of age. Correlation factor (η) was used for evaluating the correlation between the indices examined. Daily excretion of 6-oxymelatonin was found to decrease considerably in healthy men over 30 years of age, the extent of such reduction correlating with age (η= 0.48 ± 0.19, P < 0.02). Similar correlation is absent in healthy women. There is an age-related reduction in FTS in both healthy women (η= 0.63 ± 0.13, P < 0.001) and men (η= 0.57 ± 0.12 P < 0.001), although in the latter this reduction occurs 10 years earlier (beginning at 30 years) and is more pronounced. Blood cortisol levels in healthy subjects increase with age, more notably in men than in women. Agerelated changes in the content of the hormones under study are still more pronounced when patients of corresponding age groups develop neoplasms. Male patients from 20 to 29 and 30 to 49 years of age with melanoma show daily levels of 6-oxymelatonin excretion of 10.13 ± 0.71 μg/24 hr and 11.70 ± 1.26 μg/24 hr, respectively, while healthy men of the same age show much higher melatonin levels, i. e., 18.98 ± 1.36 μg/24 hr and 15.46 ± 1.13 μg/24 hr, respectively. Male melanoma patients aged 30 to 49 years have reduced log2 of FTS titers (as little as 1.44 ± 0.23) compared to that of healthy, age-matched males (3.40 ± 0.23, P < 0.05). In female patients aged 20–39 years and 40–49 years, the log2 of FTS titers was 1.96 ± 0.37 and 1.62 ± 0.25, respectively, which is significantly lower (P < 0.05) than values for healthy women of the same age (5.60 ± 0.17 and 3.60 ± 0.41). In melanoma male and female patients from 20 to 49 years of age, cortisol levels are significantly higher than the mean values for this hormone in agematched healthy subjects, being 193.18 ± 19.67 ng/ml and 135.43 ± 14.36 ng/ml, respectively (with normal levels of 140.60 ± 9.62 ng/ml and 101.03 ± 8.61 ng/ml). The results of correlation analysis indicate that daily excretion values for 6-oxymelatonin in healthy subjects correlate with both FTS titers and cortisol content, while the latter two correlate with each other (P < 0.05). Statistically significant correlation between the levels of all examined hormones was found in melanoma patients as well (P < 0.05).
TL;DR: Results are consistent with the hypothesis that the pineal gland synchronizes photoperiod‐induced blastocyst implantation in the western spotted skunk.
Abstract: Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham-superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (B1) pregnant skunks were subjected to a natural photoperiod, and the duration of the preimplantation period was monitored. In a second set of experiments, melatonin was administered to pregnant skunks via two methods to determine whether or not this pineal hormone would mimic the effects of short day photoperiods or B1 on duration of the preimplantation period. Bilateral SCGx, which presumably denervated the pineal, had no effect on the average duration of the preimplantation period (232 +/- 57 vs. 199 +/- 6 days). However, SCGx reversed the inhibitory effect of B1 on implantation as SCGx/B1 animals had an average duration of the preimplantation period that was not significantly different from intact controls (262 +/- 46 vs. 214 +/- 11 days) but was significantly shortened in comparison to enucleated animals (262 +/- 46 vs. 316 +/- 45 days). Melatonin significantly lengthened the duration of the preimplantation period in animals receiving either daily afternoon injections of melatonin or those receiving melatonin Silastic capsule implants. These results are consistent with the hypothesis that the pineal gland synchronizes photoperiod-induced blastocyst implantation in the western spotted skunk.
TL;DR: It is demonstrated that ovariectomy also has no effect on the lights on at night decrease of SNAT activity, and this study confirms that intraventricular infusion of carbachol decreases the nocturnal pinealSNAT activity.
Abstract: We have examined the nocturnal increase in pineal serotonin N-acetyltransferase (SNAT) activity in the rat and the decrease in activity of this enzyme as a result of exposure of the rats to light during the nocturnal period. In females with normal ovulatory cycles and ovariectomized females, levels of the enzyme were similar during the dark (695 +/- 70 pmol/min/gland vs. 590 +/- 68) or after 20 min of lights on at night (107 +/- 5 vs. 105 +/- 8). Carbachol, a cholinergic agonist, was injected at 2400 hr (EST) into the lateral ventricle of orbitally enucleated rats. The agonist simulated the lights on effect in both intact and ovariectomized rats. Highly purified fractions of alpha-bungarotoxin, a nicotinic cholinergic antagonist were injected into either the third ventricle or bilaterally adjacent to the SCN in intact females, intact males, or ovariectomized rats. These injections had no effect on either the nighttime increase or the lights on inhibition of SNAT. This study makes the following observations: 1) As was previously demonstrated [Illnerova, H. Endocrinol. Exp. 9:141-148, 1975], ovariectomy affects neither the daytime (light period) nor nighttime (dark period) activity of pineal SNAT. This study extends previous work by demonstrating that ovariectomy also has no effect on the lights on at night decrease of SNAT activity. 2) This study confirms that intraventricular infusion of carbachol decreases the nocturnal pineal SNAT activity [Zatz, M., and Brownstein, M.J. Brain Res. 213:438-442, 1981]. 3) This study does not confirm the report that the nicotinic cholinergic antagonist alpha-bungarotoxin prevents the loss of nocturnal SNAT activity induced by turning lights on at night [Zatz, M., and Brownstein, M.J. Brain Res. 213:438-442, 1981].
TL;DR: It is suggested that circadian fluctuations in the intensity of constant light entrain variation in the pineal gland functioning of this seal during summer, capable of transient bouts of activity during constant and bright daylight.
Abstract: Blood was collected over a 24-h period from free-living adult Weddell seals that had been exposed to natural constant daylight for some 12 weeks. The plasma melatonin concentration was low throughout the trial (range of means: 30.8-70.4 pg/ml) with the exception of a 3-h period centered on 1700 h local time, when the plasma level rose to a mean of 131.8 pg/ml. The pineal gland of the Weddell seal is thus capable of transient bouts of activity during constant and bright daylight, a situation usually inhibitory to the function of the gland. It is suggested that circadian fluctuations in the intensity of constant light entrain variation in the pineal gland functioning of this seal during summer.
TL;DR: It is suggested that physiological concentrations of estradiol may exert a postsynaptic stimulation of cyclic AMP and melatonin synthesis to the same extent in all three regions of the female guinea pig pineal complex.
Abstract: To examine the effects of estradiol, testosterone, or progesterone on cyclic adenosine 3',5'-monophosphate (AMP) accumulation, 5-methoxyindole levels, and norepinephrine (NE) release by the female guinea pig pineal complex, samples of the deep, intermediate, or superficial portions of the complex were incubated in vitro with varied concentrations of either hormone. Exposure for 10 minutes to physiological amounts of estradiol (10 nM) or to 100 microM NE increased significantly cyclic AMP levels to the same extent in the three pineal regions. A maximal effect on cyclic AMP accumulation was observed at 100-nM concentrations of estradiol, with a tendency to return to basal levels at 1-10 microM of estradiol. Only high concentrations of testosterone or progesterone (i.e., 1-10 microM) increased cyclic AMP accumulation in incubated guinea pig pineal fragments. At a 100-nM concentration estradiol did not affect NE-stimulated cyclic AMP accumulation in guinea pig pineal fragments. In samples of either pineal region incubated for 6 hours in TC 199 medium with 10(-7) M or greater concentrations of estradiol and analyzed for melatonin, 5-methoxyindoleacetic acid, and 5-methoxytryptophol by high-pressure liquid chromatography with electrochemical detection, a significant increase of melatonin levels was found. Neither testosterone nor progesterone modified 5-methoxyindole levels of incubated explants. K+-stimulated transmitter release from guinea pig pineal fragments previously incubated with 3H-NE was not affected by hormone exposure. These results suggest that physiological concentrations of estradiol may exert a postsynaptic stimulation of cyclic AMP and melatonin synthesis to the same extent in all three regions of the female guinea pig pineal complex.
TL;DR: Subcutaneous implantation of melatonin for a period of 12 weeks with reinforcement of implants every fortnight had no significant influence on photoinduced gonadal development in the pigeon.
Abstract: Subcutaneous implantation of melatonin for a period of 12 weeks with reinforcement of implants every fortnight had no significant influence on photoinduced gonadal development in the pigeon. Neither the weight of the gonads or the oviduct nor the gonadal size was affected by melatonin. Pinealectomy also was found to have no significant influence on gonadal weight when examined 20 weeks after the surgery.
The plasma levels of luteinizing hormone and testosterone were not significantly influenced by a 10-week implantation of melatonin, although a trend toward an increase (statistically insignificant) in testosterone concentration was apparent in melatonin-implanted male pigeons. Plasma concentration of estradiol was found to increase significantly in both male and female pigeons following the 10-week melatonin implantation. A trend toward an increase in plasma corticosterone level was also apparent in these melatonin-implanted birds, but the increase was statistically insignificant.
TL;DR: Results demonstrate an inhibitory pineal influence on adrenal DBH activity, and that this was dose dependent, and the inhibitory effect of exogenous melatonin on adrenomedullaryDBH activity depended upon the presence of the pineal, suggesting a mediating role of the Pineal in this particular action of melatonin.
Abstract: Pineal influence in the control of adrenomedullary function in golden hamsters was investigated by examining changes in adrenal dopamine-beta-hydroxylase (DBH) activity following pinealectomy, either alone or in combination with melatonin administration. Adult males acclimated to an LD 14:10 photoperiod were distributed in five experimental groups: intact controls (NO), sham-pinealectomized (S), sham-pinealectomized with black plastic shielding of the pineal region, pinealectomized (PX), and pinealectomized with the operated region shielded. Animals representing all of these groups were injected (between L11 and L11.75) with either vehicle, or a low dose (25 micrograms) or a high dose (2,500 micrograms) of melatonin daily for 28 days, after which they were killed, and the adrenals were collected for assay of DBH activity by means of a sensitive radioenzymatic method. We found that PX + vehicle led to increased (P less than .05) adrenal DBH activity in comparison with either NO or S groups; daily 25 micrograms of melatonin resulted in lowered DBH activity in the NO group when compared with NO + vehicle (P less than .001) or S + vehicle (P less than .001) groups; PX + 25 micrograms melatonin reversed the action of 25 micrograms melatonin in the NO + 25 micrograms group; 2,500 micrograms melatonin was without effect on adrenal DBH in any of the injected surgical groups. These results show an inhibitory pineal influence on adrenal DBH activity, and that this was dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: An increase in the number of the synaptic ribbons after stimulation of the SCG supports the hypothesis that the numerical reduction of dense cores of nerve vesicles in the cat pineal gland influences the level of synaptic ribbon formation.
Abstract: The nerve vesicles and synaptic ribbons were quantified in the cat pineal gland after electrical stimulation of the pineal sympathetic nerve fibers. It has been shown that the bilateral electrical stimulation of the preganglionic fibers innervating the superior cervical ganglia (SCG) markedly reduces the number of dense cores of small dark vesicles (SDV) and, on the other hand, modifies the number and shape of the large dark vesicles (LDV). An increase in the number of the synaptic ribbons after stimulation of the SCG supports the hypothesis that the numerical reduction of dense cores of nerve vesicles in the cat pineal gland influences the level of synaptic ribbon formation.