bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Substance P Neurons in the Epithalamus of the Rat: An Immunohistochemical Investigation
Authors: Rønnekleiv Oline K. , Kelly Martin J.
Published: February 2007

Substance P (SP) immunoreactivity was studied in the epithalamus of intact and superior cervical ganglionectomized female rats by using the peroxidase‐antiperoxidase immunocytochemical technique. Cells containing immunoreactive SP were located in the medial habenula, and SP fibers were observed in the lateral habenula, habenular commissure, pineal stalk, and the pineal organ. Bilateral removal of the superior cervical ganglia did not affect the immunocytochemical staining of SP‐containing cells and fibers 15–30 days later. It is suggested that habenular neurons containing SP send projections into the pineal organ of the rat.
Pineal Function in Burns: Melatonin Is Not a Marker for General Sympathetic Activity
Authors: Vaughan George M. , Taylor Thomas J. , Pruitt Basil A. , Mason Arthur D.
Published: February 2007

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.
Alloxan‐Induced Diabetes and the Pineal Gland: Differential Effects on the Levels of Pineal N‐Acetylserotonin, Pineal Melatonin, and Serum Melatonin
Authors: Pang S. F. , Tang F. , Tang P. L.
Published: February 2007

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°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 < 0.05) than those of the controls. Conversely, pineal and serum levels of melatonin in the control rats were significantly higher (P < 0.05) than those of the alloxan‐induced diabetics. Our 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 pineal melatonin secretion.
Pharmacological Studies on the Regulation of N‐Acetyltransferase Activity and Melatonin Content of the Pineal Gland of the Syrian Hamster
Authors: Steinlechner Stephan , King Thomas S. , Champney Thomas H. , Richardson Bruce A. , Reiter Russel J.
Published: February 2007

Thus far, all attempts to stimulate melatonin synthesis by β‐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 β‐receptors are involved in maintaining elevated melatonin levels.
Ultrastructural Studies on the Pinealocyte Mitochondria During the Daytime and at Night
Authors: Krakowski Gerhard , Cieciura Leszek
Published: February 2007

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.
In Vitro Uptake and Metabolism of [3H]Indole Compounds in the Pineal Organ of the Pike. I. A Radiochromatographic Study
Authors: Falcón Jacky , Balemans Matheus G. M. , van Benthem Jan , Collin Jean‐Pierre
Published: February 2007

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.
Influence of Subcutaneous Melatonin Implantation on Gonadal Development and on Plasma Levels of Luteinizing Hormone, Testosterone, Estradiol, and Corticosterone in the Pigeon
Authors: John T. M. , George J. C. , Etches R. J.
Published: February 2007

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.
The Influence of Melatonin on the Content of Vasopressin and Oxytocin in the Hypothalamus and Neurohypophysis in Euhydrated and Dehydrated Male Rats
Authors: Juszczak Marlena , Guzek Jan W. , Lewy Anna
Published: February 2007

Melatonin injected in a single intraperitoneal dose of 100 μg/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.
Rat Pineal Exhibits Two Electrophysiological Patterns of Response to Microiontophoretic Norepinephrine Application
Authors: Reyes‐Vazquez C. , Prieto‐Gomez B. , Aldes L. D. , Dafny N.
Published: February 2007

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.
Rhythmic Melatonin Response of the Syrian Hamster Pineal Gland to Norepinephrine In Vitro and In Vivo
Authors: Vaughan George M. , Lasko James , Coggins Sandy H. , Pruitt Basil A. , Mason Arthur D.
Published: February 2007

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 μg/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 μg/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 μg/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.
Melatonin, Thymic Serum Factor, and Cortisol Levels in Healthy Subjects of Different Age and Patients With Skin Melanoma
Authors: Grinevich Yury Akimovich , Labunetz Irina Fedorovna
Published: February 2007

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).
Effect of Melatonin on the Force of Spontaneous Contractions of In Vitro Rat Small and Large Intestine
Authors: Harlow Henry J. , Weekley Bruce L.
Published: February 2007

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.
A Once‐Repeated Study of Nocturnal Plasma Melatonin Patterns and Sleep Recordings in Six Normal Young Men
Authors: Claustrat Bruno , Brun Jocelyne , Garry Philippe , Roussel Bernard , Sassolas Geneviève
Published: February 2007

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 · 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.
Diurnal Variations of Plasma Melatonin Concentrations in Pregnant or Pseudopregnant Mink (Mustela vison) Maintained Under Different Photoperiods
Authors: Ravault J. P. , Martinet L. , Bonnefond C. , Claustrat B. , Brun J.
Published: February 2007

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.
Both Hydroxy‐and Methoxyindoles Modify Basal Temperature in the Rat
Authors: Morton Dougal J.
Published: February 2007

The various pineal gland tryptophan metabolites were administered to male rats intraperitoneally (100 μg/kg) and rectal temperatures were recorded. Of the compounds tested, hydroxytryptophan, N‐acetylserotonin, hydroxytryptophol, and their corresponding methoxyindoles all caused a marked hypothermia, indicating that several indolic products may be involved in thermoregulation. Although the brain penetration of indoles is poor, a central site of action would be most likely, although peripheral actions cannot be excluded. The mechanism of induction of hypothermia may involve peptides, the pituitary‐thyroid axis, the adrenal gland, or a combination of these. These results may suggest that the pineal gland integrates environmental cues to act in concert with physiological thermostats in the fine tuning of thermoregulation.
Diurnal Variation of Cation Pump Enzyme Activity in Pineal and Seven Other Rat Brain Regions
Authors: Bertoni J.M. , Sprenkle P.M. , Rollag M.D. , Binkley S. , Brainard G.C.
Published: February 2007

Adult female Long‐Evans rats were maintained on an automatically regulated artificial lighting schedule of light:dark (L:D) 14.5:9.5 for 12 wk. After sacrifice at 0630, 1130, 1600, 1800, 2000, 2200, 0230, or 0400, the pineals were removed, weighed, and assayed for N‐acetyltransferase (NAT), melatonin, Mg++‐paranitrophenylphosphatase (pNPPase), and K‐pNPPase activity. The brains were quickly dissected into the following areas: cerebellum, superior colliculi, inferior colliculi, visual cortex, auditory cortex, sensorimotor cortex, and the hypothalamic area around the suprachiasmatic nucleus. These regions were weighed and 10% sucrose homogenates were prepared for determinations of protein, Mg++ ‐pNPPase, and K+‐pNPPase activity. Pineal melatonin rose over six‐fold from 144 ± 70 pg/gland at 1130 to 981 ± 173 pg/gland at 0230. Similarly, pineal NAT activity rose over 11‐fold, from 119 ± 12 pmol/gland/h to 1315 ± 232 pmol/gland/h at the same times. K + ‐pNPPase activity rose by about two‐thirds, from 133 ± 12.8 nmol/gland/h to 224 ± 22.3 nmol/gland/h from 1600 to 0230. However, when expressed per mg protein, these differences in pNPPase activity were not significant. There were no significant daily rhythms discernible in any of the seven other brain regions across these times. We conclude that cation pump enzyme activity varies only slightly with time in the rat brain and pineal gland, in spite of definite daily rhythms of pineal melatonin and NAT activity.
Pinealectomy and Constant Release of Melatonin or 5‐Methoxytryptamine Induce Testicular Atrophy in the European Hamster (Cricetus cricetus, L.)
Authors: Masson‐Pévet M. , Pévet P. , Vivien‐Roels B.
Published: February 2007

The role of the pineal and of photoperiod in the regulation of gonadal activity has been studied in the European hamster, a wild hamster commonly found in the vicinity of Strasbourg, France. Besides the presence of a probable endogenous circannual rhythm in reproductive capacities, it appears that, as in all other hamster species studied to date, the sexual activity of this animal is directly regulated by changes in the photoperiodic environment.

Pinealectomy as well as a constant release of melatonin or of 5‐methoxytryptamine has no effect on the gonadal atrophy induced by short photoperiod, but induces testicular regression in animals kept under long photoperiod. The pineal in this species appears thus to be involved in the maintenance of sexual activity in long photoperiod, while it is apparently not required for the gonadal inhibitory effect of short photoperiod. These results are similar to those obtained in the Turkish hamster. 5‐Methoxytryptophol is not implicated in the phenomenon of synchronization of the sexual activity with the photoperiodic changes.
Investigation of Circadian Rhythms for Pineal 5‐Hydroxytryptophol and Other Indoles in the Rat
Authors: Foley Paul B. , Cairncross Keith D.
Published: February 2007

5‐hydroxytryptophol (5HTL) occurs in the pineal gland of the rat at levels comparable to those of melatonin, yet few studies have been conducted to investigate 5HTL as a potential alternative pineal hormone. In this study the pineals of 90‐day‐old male Sprague Dawley rats have been assayed by high performance liquid chromatography coupled with electrochemical detection. Significant (P < .0001) circadian variation was measured in 5HTL levels, and a fivefold plateau elevation occured during the middle of the light period. By comparison with the timing of the variations in N‐acetyl serotonin and melatonin levels, it is suggested that 5HTL may not be regulated by simple competition with N‐acetyl transferase for the common substrate 5HT but may, in fact, be regulated independently. Literature supporting such a suggestion, and a model incorporating it, are presented for discussion.
Multiple Forms of Arylalkylamine N‐Acetyltransferases in the Rat Pineal Gland: Purification of One Molecular Form
Authors: Namboodiri M.A.A. , Brownstein M.J. , Weller J. , Voisin P. , Klein D.C.
Published: February 2007

Rat pineal serotonin N‐acetyltransferase (EC 2.3.1.87) activity is isolated in two molecular forms (Mr≅ 10,000 95,000) by high performance size exclusion liquid chromatography in the presence of ammonium acetate (0.1 M, pH 6.5). In the presence of sodium citrate (0.1 M, pH 6.5), however, it is eluted as a single peak of intermediate size (Mr= 30,000). A highly enriched preparation of one of the molecular forms has been obtained by a two‐step purification procedure involving disulfide‐exchange anion‐exchange chromatography. The N‐acetyltransferase in 250 pineal glands obtained from isoproterenol‐treated rats can be purified about 80‐fold in 1 day; recovery is about 3%. Polyacrylamide gel electrophoresis of the final preparation indicates that a single major b(Mr≅ 11,000) is present; this appears to be serotonin N‐acetyltransferase.
Gonadal Regression Induced by Caloric Restriction Is Not Mediated by the Pineal Gland in Deer Mice (Peromyscus maniculatus)
Authors: Nelson Randy J.
Published: February 2007

The role of the pineal gland in mediating reproductive regression in response to nonphotoperiodic cues was assessed. A proportion of deer mice (Peromyscus maniculatus) undergo gonadal regression subsequent to moderate food restriction. The reproductive regression after inanition qualitatively and quantitatively resembles short‐day‐induced regression. The physiological mechanisms responsible for gonadal regression after food restriction are unknown. The hypothesis that the mechanisms underlying photoperiodic responsiveness also mediate testicular regression caused by reduced food consumption was tested. Males were pinealectomized or received sham operations. Upon recovery, food availability was restricted to 70% of ad libitum intake. After 8 weeks, the reproductive condition was examined. Pinealectomy did not prevent gonadal regression, suggesting that the pineal gland does not mediate caloric information in this species.
Metabolism Pharmacokinetics of Melatonin in the Ewe
Authors: English Judie , Bojkowski Christopher J. , Poulton Anthony L. , Symons Andrew M. , Arendt Josephine
Published: February 2007

The pineal hormone melatonin has been used to advance the onset of the breeding season in sheep thus produce lambs earlier in the year. If this reproductive manipulation is to be used commercially, some knowledge of the route of metabolism identity of possible metabolites is necessary. A major metabolite of melatonin in rodents man is 6‐hydroxymelatonin sulphate (acetyl‐methoxytryptamine‐6‐sulphate [aMT6S]). No significant amounts of this metabolite could be found in the plasma of untreated ewes. After subcutaneous implantation of melatonin for 5 months, plasma levels of aMT6S were also insignificant. On the other hand, both a single oral dose of melatonin (3 mg) daily oral dosing gave rise to circulating levels of aMT6S in the range of 150 to 1,500 pg/ml for at least 18 h. The profiles Seen after 180 days treatment were similar to those seen after a single dose, indicating that this route of melatonin metabolism is not induced by chronic administration. Intravenous injection of melatonin (200 or 20 μg) gave rise to detectable levels of aMT6S in the plasma. These results indicate that the quantitative aspects of melatonin metabolism differ according to the route of administration.
Effect of Melatonin and 5‐Methoxytryptamine on Sex Steroids and Thyroid Hormones During the Prespawning Phase of the Annual Reproductive Cycle in the Freshwater Teleost, Clarias batrachus
Authors: Nayak P.K. , Singh T.P.
Published: February 2007

Melatonin and 5‐methoxytryptamine have been studied in the freshwater teleost Clarias batrachus during the prespawning period. The data have provided evidence of the inhibitory effects on sex steroids and thyroid hormones when the pineal indoleamines melatonin and 5‐methoxytryptamine (5‐MT) are administered intramuscularly daily in the afternoon for 27 days. The different dose levels had different effects. The higher dose levels of melatonin showed the initiation of counter inhibitory impacts on testosterone and T3, T4 levels. The melatonin acted more effectively than 5‐MT.
Effects of Photoperiod or Exogenous Melatonin Administration on the Activity of N‐Acetyltransferase and Hydroxyindole‐O‐Methyltransferase and the Melatonin Content of the Harderian Gland of Two Strains of Female Syrian Hamsters
Authors: Menendez‐Pelaez Armando , Santana Celsa , Howes Kimberly A. , Sabry Ismail , Reiter Russel J.
Published: February 2007

The activities of N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT) and the melatonin concentration of the Harderian glands of two strains of Syrian hamster females (outbred and inbred LSH/SsLak) exposed to two different photoperiods (14:10 h and 8:16 h) were studied. The Harderian glands of the inbred hamsters showed greater NAT activity than those of the outbred animals. On the other hand, the glands of the outbred hamsters exhibited higher HIOMT activity and melatonin content than those of the inbred LSH/SsLak. Short photoperiod exposure, which produced gonadal regression in the inbred but not in the outbred hamsters, decreased the NAT activity in the inbred animals to the levels of the outbred. HIOMT activity was not affected by the lighting conditions. After the exposure to short days, the melatonin content of the inbred hamster Harderian glands increased to that in the outbred animals. Daily melatonin injections, which caused gonadal regression in the LSH/SsLak but not in the outbred hamsters, did not simulate the effect of the short photoperiod on the Harderian gland NAT activity and melatonin content of the inbred hamsters.
Role of Pineal and Eyes in the Regulation of Ovarian Activity and Vitellogenin Levels in the Catfish Exposed to Continuous Light or Continuous Darkness
Authors: Garg S. K.
Published: February 2007

To investigate the relative importance of pineal and eyes in ovarian activity, catfish subjected to pinealectomy, blinding, or both were exposed to continuous light (LL) or continuous darkness (DD) during the different phases of the annual reproductive cycle. Pineal or eyes have no influence on ovarian activity during the preparatory, prespawning, and spawning periods of the annual reproductive cycle under these photoregimes. However, the pineal accelerated ovarian activity under LL and DD during the postspawning period. Blinding alone has no effect on ovarian recrudescence under these regimes. However, combined surgery (blinded‐pinealectomy) inhibited ovarian development under both these conditions, indicating that the pineal organ is more important than the eyes. Ovarian recrudescence occurred even in the absence of both pineal and eyes, indicating the involvement of extrapineal and extraocular photoreception in the regulation of reproductive activity in the catfish.
Melatonin Effects on Prolactin Secretion in Pituitary‐Grafted Male Rats
Authors: Villanua M.A. , Agrasal C. , Tresguerres J.A.F. , Vaughan M.K. , Esquifino A.I.
Published: February 2007

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary‐grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary‐grafted rats, whereas a marked increase was detected in sham‐operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham‐operated animals. Luteinizing hormone‐releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle‐treated, sham‐operated or grafted rats, as well as in melatonin‐treated sham‐operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham‐operated and grafted vehicle‐treated rats. No PRL response could be detected in sham‐operated, melatonin‐treated animals after EB administration. In pituitary‐grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.
Human Melatonin Suppression by Light is Intensity Dependent
Authors: Mclntyre Iain M. , Norman Trevor R. , Burrows Graham D. , Armstrong Stuart M.
Published: February 2007

Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200–350 lx) may be more suitable to dichotomize patient groups from control subjects.
Evidence of High Concentrations of Melatonin in Lateral Ventricular Cerebrospinal Fluid of Sheep
Authors: Shaw Paul F. , Kennaway David J. , Seamark Robert F.
Published: February 2007

In this study we examined the cerebrospinal fluid (CSF) for regional differences in the concentration of melatonin. Cerebrospinal fluid samples were collected at hourly intervals from either the lateral ventricle or the cisterna magna of nine Merino ewes and were compared against jugular plasma. The study revealed that the CSF of the cisterna magna and the lateral ventricle had temporal patterns of melatonin that were similar to those found in jugular plasma. However, the concentrations of melatonin within the CSF obtained from the lateral ventricle were one order of magnitude higher than those of the jugular plasma, as verified by gas chromatography and mass spectrometery, while the melatonin concentrations within the CSF obtained from the cisterna magna were comparable to those of the jugular plasma. The data from this study suggest that there may be regional differences in the concentration of melatonin within the CSF and indicate that this medium is an important route of transport for melatonin from the pineal gland to putative target tissues.
Histopathologic Features of DMBA‐Induced Mammary Tumors in Blind‐Underfed, Blind‐Anosmic, and Blind Cold‐Exposed Rats: Influence of the Pineal Gland
Authors: Cos S. , Garijo F. , Corral J. , Mediavilla M.D. , Sánchez‐Barcelo E J.
Published: February 2007

The influence of the pineal gland on the histopathologic changes induced in mammary glands by 7, 12‐dimethylbenz(a)‐anthracene (DMBA) has been studied. To achieve the maximum expression of pineal action in animals, 28‐day‐old female Sprague‐Dawley rats were subjected to one of the following treatments: blindness + olfactory bul‐bectomy (BA), blindness + underfeeding (BU), or blindness + cold exposure (BC). Half of the rats in each group were also pinealectomized. Animals that were intact or only pinealectomized served as controls. Each animal received a single intragastrical dose of DMBA (20 mg) 4 weeks after performing the treatments mentioned above. At 28 weeks of age animals were sacrificed, and mammary tumors as well as mammary glands without macroscopic lesions were collected. Animals of the BU group failed to develop any tumors throughout the 20‐week control period. In the remaining groups, tumors were found; the relation between number of adenocarcinomas (AC) and fibroadenomas was similar, always with a greater incidence of ACs. Some ACs showed areas with changes in the ductal epithelium that are considered signs of tumoral regression; pinealectomized animals had the lowest incidence of ACs with signs of regression. Ductule hyperplasia, considered as a premalignant lesion, was more frequent in pinealectomized rats than in controls and in animals with enhanced pineal function (BA, BU, and BC). Some nontumoral mammary glands showed dysplastic lesions; these lesions were less frequent in BU rats than in controls. We conclude that suppression of pineal function sensitizes the ductule cells to the initiation of neoplastic processes and hinders the development of regressive changes.
Effect of Pinealectomy on the Histology of the Adrenocortical Homologue and Plasma Cortisol Level in the Indian Catfish, Heteropneustes fossilis (Bloch)
Authors: Agha A.K. , Joy K.P.
Published: February 2007

In Heteropneustes fossilis, the adrenocortical cells were highly active, hypertrophied, and degranulated after 15 and 30 days of pinealectomy in spawning/postspawning phase. Besides, several cells had undergone pycnotic changes in the 30‐day group. The plasma Cortisol level increased significantly (P < 0.05) in the pinealectomized fish in comparison to those of the sham pinealectomized and unoperated control fish. The increase was higher in the 15‐day group than in the 30‐day‐pinealectomized group. The results suggest that the pineal organ exerts an inhibitory influence on the activity of the adrenal in the catfish.
Bovine Pineal Tripeptide Threonylseryllysine Retards Puberty in Female Rats
Authors: Benson Bryant
Published: February 2007

When injected into rodents, the bovine pineal tripeptide threonylseryllysine (TSL) elicits diverse antireproductive effects in a number of animal models. Extensive studies of its effects on pubertal development have not been carried out, however. In the present study, 1.0 μg of T‐S‐L was administered daily to female Charles River CD rats throughout the peripubertal period, and effects on vaginal opening time, ovarian histology, and serum luteinizing hormone (LH) levels were observed. Since TSL is known to alter the action of luteinizing hormone releasing hormone (LHRH), it was postulated that this antireproductive tripeptide would delay the time of vaginal opening associated with first ovulation. Two hundred eighty‐seven weanling females were housed at 22°C under a 14L:10D photoperiod. They were divided into three groups for daily intraperitonal injections of either saline (SAL), 1.0 μg TSL, or 5.0 μg melatonin (aMT) beginning on the 23rd day of life. Subgroups of nine to ten rats from each treatment group were sacrificed on days 28, 30, 32, 33, 34, 35, 36, 37, 38, and 40. Although the body weights of all animals increased significantly during the course of the study, no significant differences were observed in this parameter among rats treated with saline, aMT, or TSL. Vaginal opening time was significantly delayed by TSL between days 32 and 40, and uterine weights were significantly lower in this group. Prepubertal increases in serum levels of LH were also significantly reduced. At the dose utilized, aMT was without significant effects on these parameters. Rats sacrificed between 32 and 38 days of age were classified on the basis of uterine weights and ovarian histology as either anestrous or in early proestrus, late proestrus, or estrus. Compared with the SAL‐ or aMT‐treated groups, TSL treatment increased the percentage of animals in both anestrus and early proestrus. At the dose utilized the bovine pineal peptide TSL effectively delayed the onset of puberty, probably through its known inhibitory action on gonadotropin secretion. This observation may reflect the demonstrated ability of TSL to bind to LHRH in a sequence‐ and residue‐specific manner, resulting in modulation of this peptide's gonadotropin releasing activity.
Role of Postsynaptic α‐Adrenergic Receptors in the β ‐Adrenergic Stimulation of Melatonin Production in the Syrian Hamster Pineal Gland in Organ Culture
Authors: Santana Celsa , Guerrero Juan M. , Reiter Russel J. , Menendez‐Pelaez Armando
Published: February 2007

The role played by postsynaptic α‐adrenergic receptors in the stimulation of pineal melatonin production was investigated in the Syrian hamster. The studies were conducted using organ cultured pineal glands collected from both anatomically intact and superior cervical ganglionectomized hamsters. Results obtained indicate that phenylephrine, an a‐adrenergic agonist, by itself has no effect in promoting melatonin production; however, it potentiates the stimulatory effects of isoproterenol, a P‐adrenergic agonist, on pineal melatonin production in nonoperated hamsters. Similar observations were obtained with pineal glands whose presynaptic terminals were removed by prior superior cervical ganglionectomy. However, a longer incubation time was required (4–6 hours vs. 2 hours) with pineal glands taken from ganglionectomized animals. Apparently, β‐adrenergic activation is an absolute requirement to stimulate pineal melatonin production, and an a‐adrenergic receptor mechanism potentiates P‐adrenergic activation. In addition, the findings obtained with denervated pineal glands suggest that the regulation of pineal melatonin production by both α‐ and p‐adrenergic mechanisms is through receptors located on postsynaptic structures.
Predominant Cytosolic Distribution of Serotonin in Rat Pineal Gland in Contrast to Biogenic Monoamine Localization in Midbrain and Adrenal Gland
Authors: Boschi Gabrielle , Scherman Daniel , Rips Richard
Published: February 2007

The subcellular distribution of serotonin and norepinephrine in the rat pineal gland was studied by tissue fractionation and compared with that of biogenic monoamines in the adrenal gland and midbrain. Homogenized tissues were fractionated by ultracentrifugation or by filtration through cellulose ester membranes. Most of the epinephrine (70‐80%) and norepinephrine (62‐82%) present in the adrenal glands was detected in the particulate fraction. The same distribution was found for serotonin (68. 5%) and norepinephrine (59%) in the midbrain and for norepinephrine (62. 5%) in the pineal gland. However, most of the serotonin in the pineal was found in the soluble fraction (895–98%). This suggests that the great majority of serotonin in the rat pinealocytes is cytosolic and thus is not stored in subcellular vesicles, in contrast to the biogenic monoamines in the midbrain or adrenal gland.
Kinetic Study of Melatonin Release From Rat Pineal Glands Using a Perifusion Technique
Authors: Simonneaux V. , Ouichou A. , Pévet P. , Masson‐Pévet M. , Vivien‐Roels B. , Vaudry H.
Published: February 2007

In previous studies, noradrenaline was found to elicit a rise of melatonin secretion through activation of typical P‐adrenergic receptors. In the present study, a perifusion system was developed to characterize the kinetics of melatonin release from rat pineal glands. Isolated pineal glands from adult male rats were continuously perifused for 15 h in a Krebs‐Ringer solution, and the concentration of melatonin in the effluent perifusate was monitored using a specific radioimmunoassay. The rate of release of melatonin declined during the first 3–4 h of perifusion and then remained fairly stable for at least 11 h. The spontaneous release of melatonin was around 20 pg per min and per gland. When pineal glands were stimulated with isoproterenol, melatonin release output linearly increased for at least 2 h after the stimulation. The increase in melatonin release depended on the isoproterenol concentration and on the duration of the stimulation. The analysis of the pattern of melatonin secretion by a single rat pineal gland showed that the secretion was irregular but did not present a clear feature of pulsatile or oscillatory release over all h‐long study. The perifusion system was found useful in order to follow the characteristics of melatonin release from pineal glands and should allow investigations of neuronal or hormonal control of pineal gland activities.
Melatonin and Pituitary‐Gonadal Function in Disorders of Eating Behavior
Authors: Ferrari E. , Foppa S. , Bossolo P.A. , Comis S. , Esposti G. , Licini V. , Fraschini F. , Brambilla F.
Published: February 2007

In order to study the possible relationships between melatonin secretion and pituitary‐gonadal function, the circadian rhythm of plasma melatonin, the basal levels of estradiol‐17p and testosterone and the luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) response to luteinizing hormone‐releasing hormone (LH‐RH) stimulation were evaluated in normally cycling healthy women and in two groups of women with menstrual dysfunctions related to eating disorders (19 patients with anorexia nervosa and 16 with primary obesity). The circadian rhythm of plasma melatonin reached statistical significance in anorectic patients but not in obese patients. The mean 24 h melatonin level was significantly higher in anorectic than in obese patients and in control subjects. However, both groups of patients shared some abnormalities of melatonin circadian pattern, such as increased ratio between day and night melatonin levels, abnormal secretory peaks during the light hours and great interindividual variability for timing, amplitude, and duration of melatonin nocturnal peak. A selective impairment of LH secretion was observed in both anorectic and obese patients. By considering together the two groups of patients and controls, a linear inverse correlation between the circadian mesor of plasma melatonin and the basal and LH‐RH stimulated LH levels was found. The persistence of a certain melatonin secretion during the light hours in both anorectic and obese patients could play an inhibitory role on the pituitary‐gonadal function in these subjects.