bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Differences in Norepinephrine and Dopamine Concentration and Effect on Serotonin Uptake and Release in Bovine Pineal Gland
Authors: Chuluyan Héctor E. , Rosenstein Ruth E. , Stern Javier , Cardinali Daniel P.
Published: February 2007

In order to analyze whether the bovine pineal gland is a homogeneous or a heterogeneous structure as far as monoamine content, the regional differences in norepinephrine (NE), dopamine (DA), serotonin (5HT), and 5‐hydroxyindoleacetic acid (5HIAA) contents were assessed by high‐pressure liquid chromatography. NE content was maximal in the proximal (close to the recessus pinealis) region and decreased in a rostral‐caudal direction to achieve minimal values at the distal region. DA exhibited an opposite trend to NE, NE/DA ratios varying from 3.2 (proximal region) to 1.4 (distal region). Significantly lower NE content was found at the inferior as compared to the superior pineal region, and at the cortex as compared to the medulla. No significant differences were detected in DA concentration of these latter pineal regions, or in 5HT or 5HIAA concentration as a function of the region examined. 3H‐5HT and 3H‐NE uptake were maximal at the proximal zone in a rostral‐caudal direction, at the superior as compared to the inferior region, and at the medulla as compared to the cortex. Unlabeled NE was equally effective to compete with 3H‐5HT uptake in the several pineal regions studied. While NE increased maximally 3H‐5HT release in a rostral‐caudal direction, DA exhibited an opposite trend, displaying maximal 5HT release activity at the distal pineal region. DA and NE 5HT‐releasing activity were greater in the pineal medulla than in the cortex, and did not exhibit differences in the superior as compared to the inferior pineal aspects. Excess (55 mM) K+ released 3H‐5HT to a similar extent regardless of the pineal region examined.
Effects of Season, Pinealectomy, and Blinding, Alone and in Combination, on Hypothalamic Monoaminergic Activity in the Teleost Channa punctatus (Bloch)
Authors: Khan I. A. , Joy K. P.
Published: February 2007

In Channa punctatus, day‐night variations in hypothalamic 5‐HT (serotonin) and monoamine oxidase (MAO) activity were noticed in preparatory but not other phases (prespawning and postspawning) of the annual reproductive cycle. Hypothalamic MAO, 5‐HT, and norepinephrine (NE) activity was found to be high in the prespawning phase and low in the postspawning phase. Dopamine (DA) activity, on the other hand, was high in the postspawning season and low in the prespawning phase. Pinealectomy caused season‐dependent effects on hypothalamic monoaminergic activity, with a significant increase in serotonergic activity and a significant reduction in MAO activity at midscotophase during the preparatory phase (March) but not in the prespawning (May‐June) or postspawning (September) phases. Hypothalamic catecholaminergic (CA) activity was not influenced by pinealectomy during any of the seasons. To determine whether or not the photoperiodic influences on daily variations of 5‐HT and MAO in the preparatory phase are mediated via pineal and/or lateral eyes, fish were pinealectomized and/or blinded in January, when there is no rhythm, and sacrificed in February, when a day‐night variation normally sets in. The day‐night difference in 5‐HT content and activity and MAO activity was not abolished by pinealectomy or blinding alone; but the combination (pinealectomy + blinding) obliterated the daily variation only in 5‐HT content and in MAO activity. However, pinealectomy and blinding, alone or in combination, caused a significant elevation of 5‐HT activity (not its level) and a significant decrease in MAO activity at midscotophase, with the combination having an additive effect. Hypothalamic CA content or activity was not affected by these regimes. The results show that photoperiodic influence on the daily pattern of 5‐HT and MAO activity is mediated through and by the interaction of the pineal and lateral eyes.
Alpha‐1 Adrenoceptor Involvement in the Control of Melatonin Secretion in the Golden Hamster
Authors: Stankov Bojidar , Lucini Valeria , Mariani Marco , Scaglione Francesco , Demartini Germana , Fraschini Franco
Published: February 2007

The nocturnal peak in pineal and serum melatonin content was reduced following administration of the selective alpha‐1 adrenoceptor antagonist prazosin in a dose of 0.25 mg/kg. The effect was pronounced one hour post treatment during the late dark phase of the daily photocycle. These data confirm the reported findings that the hamster pineal sensitivity to adrenergic challenge is confined to the second part of the dark phase and indicate that postsynaptically located alpha‐1 adrenoceptors are also involved in the physiological control of melatonin synthesis and/or release in that species.
Choline Acetyltransferase in Bovine Pineal Gland
Authors: Phansuwan‐Pujito P. , Govitrapong P. , Ebadi M.
Published: February 2007

Recent studies from our laboratories have shown that the bovine pineal gland contains a muscarinic cholinergic receptor with a Kd value of 0.423 ± 0.010 nM and a Bmax value of 69.75 ± 20.91 fmol/mg protein. In order to substantiate further the possible existence of a pineal cholinergic transmission, we have measured the activity of choline acetyltransferase and delineated its kinetic properties in the bovine pineal gland. This enzyme exhibited an activity of 0.0339 ± 0.0042 nmol/mg protein/min. Furthermore, the bovine pineal choline acetyltransferase possessed a Km, value of 124.86 ± 24.06 μM and a Vmax value of 0.0598 ± 0.0034 nmol/mg protein/min for acetyl CoA, and a Km value of 3.11 ± 0.94 mM and a Vmax value of 0.0155 ± 0.0016 nmol/mg protein/min for choline. The presence of muscarinic cholinergic receptors along with a specific choline acetyltransferase are supportive evidences that the bovine pineal gland may receive cholinergic innervation.
Effects of Long‐Term, Low‐Dose, Time‐Specified Melatonin Administration on Endocrine and Cardiovascular Variables in Adult Men
Authors: Terzolo Massimo , Piovesan Alessandro , Puligheddu Barbara , Torta Mirella , Osella Giangiacomo , Paccotti Piero , Angeli Alberto
Published: February 2007

Six healthy adult male volunteers underwent serial blood drawings at 4‐hour intervals over 24 hours for the definition of melatonin (MT), prolactin (PRL), cortisol, and testosterone circadian patterns. Serum levels of triiodotironine (T3) and thyroxine (T4) were determined at 0800. Systolic and diastolic blood pressure and heart rate were automatically recorded every 30 minutes for 24 hours. The responses of luteinizing hormone (LH), follicle stimulating hormone (FSH), PRL, thyroid stimulating hormone (TSH), cortisol, and aldosterone to a stimulation test with gonadotrophinreleasing hormone (Gn‐RH), thyrotrophin‐releasing hormone (TRH), adrenocorticotrophin (ACTH), and testosterone to human chorionic gonadotrophin (HCG) were also evaluated. The same protocol was repeated after a two‐month course of treatment with MT, 2 mg per os daily at 1800. After treatment, we recorded a marked elevation of mean serum MT levels with a significant phase‐advance of its circadian rhythm. The 24‐hour patterns of cortisol and testosterone displayed an anticipation of the morning acrophase of about 1.5 hour (not significant) for cortisol and three hours (P < 0.05) for testosterone. PRL pattern was unchanged as well as serum levels of thyroid hormones. The circadian organization of the cardiovascular variables did not show any changes after MT supplementation; the pituitary, adrenal, and testicular responses to specific stimuli were comparable before and after treatment. These results are compatible with the view that the MT signal may provide temporal cues to the neuroendocrine network for the organization of testicular circadian periodicity.
The Pineal Gland in Newborn Southern Elephant Seals, Mirounga leonina
Authors: Little Gerald J. , Bryden M. M.
Published: February 2007

In the newborn southern elephant seal the pineal gland is very large, and both pineal and plasma melatonin concentration is elevated. The pineal gland was investigated during the first 24 h, and up to 20 days of age, in elephant seal pups. A primary aim of this investigation was to determine whether there are obvious ultrastructural characteristics of pinealocytes that are exhibiting extraordinarily high levels of activity. Blood and pineal glands were collected from thirty seven pups of known age which were sampled at random from early September to early November (1985) at Macquarie Island. The pineal gland is large (mean weight, 4.71 ± 0.35 gm, range 1–9.3 gm) and actively secreting melatonin at birth. Melatonin concentrations were extremely variable, yet very high in pups during the first 24 h post‐partum. Mean melatonin plasma concentration for pups 0–24 h was 17632.8 ± 5723.8 pmol/l (4090.8 ± 1327.9 pg/ml), ranging from 126 pmol/l (29 pg/ml) to 297000 pmol/l (68904 pg/ml). Electron microscopic examination did not reveal any marked changes in pinealocyte ultrastructure suggestive of increased secretory activity during this period. The large and extremely active pineal gland in newborn southern elephant seal suggests that it is actively involved in thermoregulation.
Circadian Variations in Plasma Melatonin, FSH, LH, and Prolactin and Testosterone Levels in Infertile Men
Authors: Karasek M. , Pawlikowski M. , Nowakowska‐Jankiewicz B. , Kolodziej‐Maciejewska H. , Zieleniewski J. , Cieslak D. , Leidenberger F.
Published: February 2007

Circadian patterns of plasma melatonin, FSH, LH, prolactin, and testosterone were studied in 10 healthy men, 20 men with oligozoospermia, and 8 men with azoosper‐mia. Circadian rhythms were found in concentrations of melatonin and prolactin, with higher values at night in comparison with daytime levels. In patients with oligozoospermia and azoospermia an elevation in melatonin levels was observed, and an increase in melatonin concentrations occurred before onset of darkness (i. e., at 2000 h). Levels of FSH, LH, and prolactin were elevated in infertile patients. The possibilities that an increase in melatonin concentrations is either the primary feature that leads to the regression of the seminiferous epithelium or is secondary and depends on elevated gonadotropins and/or prolactin levels are discussed.
A Study of Heart‐Pineal Interactions: Atrial Natriuretic Peptide Response to Melatonin Administration in Healthy Humans
Authors: Lissoni P. , Pelizzoni F. , Perego M. , Fondrini G. , Grugni G. , Guzzaloni G. , Morabito F.
Published: February 2007

It is known that the pineal hormone melatonin plays a role in the regulation of several biological functions. In an attempt to investigate interactions between the pineal and the cardiac endocrine activity, in this preliminary study we have evaluated the effect of melatonin on the secretion of the cardiac hormone, atrial natriuretic peptide (ANP). The study included five healthy volunteers, and melatonin was given orally at a dose of 30 mg at 17:00. The results of the study show that the administration of melatonin does not influence ANP plasma concentrations. Further studies will be required to better define the cardiac‐pineal interaction.
Tumor‐Inhibiting Activity in the Rat Pineal Gland Displays a Circannual Rhythm
Authors: Bartsch H. , Bartsch C. , Gupta D.
Published: February 2007

The aim of this study was to investigate whether the tumor‐inhibiting activity present in the rat pineal gland undergoes seasonal fluctuations as do other pineal substances. Crude ethanol extracts of rat pineal glands were tested for tumor‐inhibiting activity in an in vitro microbioassay using human erythroleukemia cells which could not be inhibited by melatonin. Highest activity was detected in summer and least inhibition and even stimulation were observed in winter. There were no differences in activity between animals of different age, sex, or strain. Therefore, season seems to be the factor that exerts the most important influence on the content of tumor‐inhibiting activity in the rat pineal gland. Correlation with seasonality in the occurrence of cancer is discussed.
Effects of Pinealectomy on the Mitotic Activity of Adrenomedullary Chromaffin Cells in Relation to Time of Day
Authors: Kachi T. , Quay W. B. , Banerji T. K. , Imagawa T.
Published: February 2007

The frequency of mitoses of adrenaline (A) cells and noradrenaline (N) cells in the adrenal medulla of nonoperated (NO), sham‐operated (SPX), and pinealectomized (PX) male, 53‐day‐old Holtzman rats (n = 133) was investigated by means of light microscopy. Animals were killed at eight time points during a standardized 24‐h light‐dark (12:12) cycle 14 days after surgery. Mitotic indices (n/1,000) were determined in sections of adrenal medulla fixed with glutaraldehyde and OsO4. Overall frequency of mitoses was extremely low (mitotic index: 0.73 = 115/157,223). Daily mean mitotic index was maximum in A cells (0.83) and minimum in N cells (0.52) of PX group but did not show statistically significant differences between cell types or experimental groups. Neither cell type in NO animals showed 24‐h changes in mitotic index, but cells in SPX animals did, with highest value in the late dark phase and lowest in the late light phase, when values of two cell types were combined (P<0.01–0.001). In PX animals, mitotic index followed a similar but more distinct 24‐h change in A cells (P<0.009), but not in N cells, resulting in different time‐of‐day changes between two types of cells (P<0.01–0.05). The mitotic index was higher in PX than in control (NO and SPX) animals in the middark phase (P<0.05) and lower in operated (SPX and PX) than in nonoperated (NO) animals from late light to the early dark phase, suggesting that the latter was possibly due to a residual effect of the surgery. These results are consistent with the interpretation that the pineal has an inhibitory action on A cells and may coordinate the two types of cells in their mitotic activity, especially in the middark phase of the daily cycle.
Effect of 6‐Methoxy‐2‐Benzoxazolinone on the Activities of Rat Pineal N‐Acetyltransferase and Hydroxyindole‐O‐Methyltransferase and on Melatonin Production
Authors: Daya Santy , Pangerl Brigitte , Pangerl Andreas , Troiani Maureen E. , Reiter Russel J.
Published: February 2007

A naturally occurring compound, 6‐methoxybenzoxazolinone (6‐MBOA), present in grasses, has been shown to induce sexual maturation in a number of rodent species. The structural similarity of 6‐MBOA and melatonin has led researchers to suspect that 6‐MBOA might induce its progonadal effects by directly altering pineal function. Previous studies have shown that 6‐MBOA has the properties of a weak β‐adrenergic agonist capable of stimulating rat pineal N‐acetyltransferase (NAT) activity at pharmacological concentrations of 10−3 M. In the present study we have examined the effect of 6‐MBOA on both the pineal melatonin synthesizing enzymes, namely. NAT and hydroxyindole‐O‐methyltransferase (HIOMT) as well as on melatonin production, in organ cultured rat pineal glands. In addition, we have also examined the ability of 6‐MBOA to displace a ligand from rat brain α‐and β‐adrenoceptors. Our results confirm that 6‐MBOA stimulates NAT activity and melatonin production at the high concentration of 10−3 M. It appears to have no effect on HIOMT activity. A competition study shows that 6‐MBOA is able of displacing ligands at the α‐and β‐adrenoceptors but only at concentrations greater that 10−4 M. Whether such high concentrations of 6‐MBOA reach the pineal of rodent in their natural habitat is unknown. However, if 6‐MBOA does mediate progonadal effects by altering pineal function it would be expected that 6‐MBOA would ultimately inhibit the effects of melatonin. The possibilities are that the high melatonin levels induced by 6‐MBOA cause desensitization of melatonin receptors or that 6‐MBOA is an antagonist at the level of the melatonin receptor, thus restricting the inhibitory effects of melatonin on the reproductive system.
Effects of Melatonin on Gonadal Steroids and Glucose Plasma Levels in Frogs (Rana perezi and Rana temporaria)
Authors: Alonso‐Bedate Mercedes , Carballada Rosa , Delgado Maria Jesus
Published: February 2007

The effect of melatonin treatment on the Gonosomatic Index (GSI), ovarian germinal epithelium, plasma estradiol and testosterone levels was studied in Rana perezi females in December. No significant changes were observed in GSI, estradiol, and testosterone levels in melatonin treated animals when compared with saline injected controls, but the percentage of previtellogenic follicles decreased in animals treated with melatonin (100 μg). The effect of melatonin treatment on glucose level was studied in Rana perezi females in December and Rana temporaria males in February. In Rana perezi no significant differences were observed between melatonin treated and control animals; however, significant reductions by melatonin treatment were obtained in Rana temporaria. The possibility that the inhibitory effect of melatonin can be observed only when gonadal function and metabolism are stimulated by temperature is discussed.
Changes in Indole Metabolism in Organ Cultured Rat Pineal Glands Induced by Interferon‐γ
Authors: Withyachumnarnkul Boonsirm , Nonaka Keico O. , Attia Ahmed M. , Reiter Russel J.
Published: February 2007

The purpose of this study was to test the effects of recombinant rat interferon‐γ (IFN‐γ) on rat pineal function in orgran culture. The glands were pre‐incubated with IFN‐γ (50, 100, and 1,000 antiviral units/ml) for two hours, followed by a stimulation with isoproterenol (ISO, 10‐6M) (in the presence of IFN‐γ) for an additional three hours. The effect of IFN‐γ alone on the pineal function was also tested by adding another group incubated with IFN‐γ (1,000 antiviral units/ml) without ISO stimulation. The following parameters were estimated at the end of the incubation: the activities of N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT), the levels of melatonin, 5‐hydroxytryptophan (5HTP), 5‐hydroxytryptamine (5HT), and 5‐hydroxyindole acetic acid (5HIAA), and the 5HT/5HIAA ratio. IFN‐γ had no effect on either NAT or HIOMT activities in the pineal glands. At 50 units/ml, IFN‐γ increased the melatonin content over the ISO‐stimulated level in the pineal but not in the media. IFN‐γ alone, at 1,000 units/ml, also increased the melatonin content significantly over the control level. The levels of 5HTP and 5HIAA were significantly suppressed by IFN‐γ, either alone or in combination with ISO. The level of 5HT was not altered by any of the treatments. The 5HT/5HIAA ratio was significantly increased by IFN‐γ, either when given alone or when given in combination with ISO. The results suggest that IFN‐γ enhances melatonin production in the pineal gland by suppressing the oxidative deamination of 5HT to 5HIAA and shunting the biosynthetic pathway toward melatonin production.
“Synaptic” Ribbons in the Pineal Gland of the Horse
Authors: Karasek M. , Cozzi B.
Published: February 2007

Previous studies on the ultrastructure of the horse pineal gland did not report the presence of “synaptic” ribbons, functionally enigmatic pinealocyte organelles regularly occurring in other mammalian species. The aim of the present study was to reinvestigate the horse pinealocyte in this respect. Careful investigations here reported allowed detection of “synaptic” ribbons in the pinealocytes of all the examined animals, although in a relatively low number (5.4 ± 2.0 per 20,000 μ2 of pineal tissue; mean ± SD). The ultrastructure of “synaptic” ribbons in pinealocytes of the horse resembles closely that observed in other mammalian species.
Chronic Administration of Pineal Peptides Change the Circadian Locomotor Activity and Time‐Course of Forced Swimming in Rats
Authors: Arushanian Edward B. , Baturin Vladimir A. , Ovanesov Karen B.
Published: February 2007

After chronic administration of epithalamin (a pineal peptide drug), an increase in the amplitude and shifts in the acrophase of rat's circadian locomotor activity to late hours were observed. These results were obtained only in rats with low initial amplitude of their circadian rhythm. Epithalamin also changed the time‐course of forced swimming and decreased the rhythmic index of depression. These observations suggest that the pineal gland of the rat, via its peptides, may prevent the development of depressive‐like events.
Plasma melatonin in the Adelie penguin (Pygoscelis adeliae) under continuous daylight in Antarctica
Authors: Cockrem J.F.
Published: February 2007

Cockrem JF, Plasma melatonin in the Adelie penguin (Pygoscelis adeliae) under continuous daylight in Antarctica. J. Pineal Res. 199 1 10:2‐8.

Circadian rhythms of melatonin secretion in birds are influenced by daylength and light intensity. Daily patterns of melatonin secretion were examined in Adelie penguins (Pygoscelis adeliae) under natural continuous daylight at Cape Bird, Antarctica (77$S). Although daylight is continuous during the Antarctic summer there was a marked daily cycle of light intensity. However, there was no relationship between mean plasma melatonin levels and time of day in groups of 2–10 penguins sampled at 2–3 h intervals in November, December, or January. Mean melatonin levels over 24 h in groups of birds from which single samples were collected, or in groups of birds sampled repeatedly through cannulae, were low (12.4 ± 1.2 pg/ml‐28.8 ± 4.4 pg/ml for 4 sampling periods; n = 22‐163). Levels in individual birds were, however, quite variable and ranged from 5.0–68.1 pg/ml. Some birds had periods of increased melatonin levels that tended to occur during the time of day when light intensity was least. One bird had a clear low amplitude melatonin rhythm with a peak during the time of least light intensity. These results, the first for any bird under a natural photoperiod, indicate that melatonin secretion is inhibited by natural continuous daylight, but that it is not abolished.
Human nocturnal blood melatonin and liver acetylation status
Authors: Smith John A. , Helliwell Philip S. , Isdale Amanda , Astbury Carol , Padwick David J. , Bird Howard A.
Published: February 2007

Smith JA, Helliwell PS, Isdale A, Astbury C, Padwick DJ, Bird HA. Human nocturnal blood melatonin and liver acetylation status. J. Pineal Res 199 1 : 10: 14‐1 7.

The human dark phase melatonin concentrations exhibit a wide range of values. In an attempt to explain this variation, we measured 2250–2305 h melatonin levels by radioimmune assay in eleven fast and eleven slow acetylator phenotypes. No statistical difference between the two groups existed, suggesting therefore that such variations are not due to acetylator status. The study revealed a negative relationship between body weight or area and nocturnal melatonin concentration. No correlation was found between dark phase melatonin levels and age, anxiety, depression, or sleep rating.
Effect of dose and time of melatonin injections on the diurnal rhythm of immunity in chicken
Authors: Skwarlo‐Sońta Krystyna , Thaela Mary‐Jane , Gluchowska Boźena , Stȩpień Diana , Jagura Monika
Published: February 2007

Skwado‐Solita K, Thaela M‐J, GXuchowska B, Stepien D, Jagura M. Effect of dose and time of melatonin injections on the diurnal rhythm of immunity in chicken. J Pineal Res 1991: 10:3&35.

The effect of daily melatonin injections on the diurnal rhythm of immune parameters was examined in White Leghorn cockerels, kept from hatching in L:D 12:12 conditions. Subcutaneous injections of melatonin were made at the beginning of darkness or 4 h earlier for four weeks starting from one week of life. The melatonin dosage in one group was raised (10, 13, 16, and 20 ng per bird daily, respectively) during four consecutive weeks. The two other doses were 10 and 500 times higher and were increased every week as well. Control birds received equivalent injections of vehicle. Three‐week‐old chickens were immunized ip with sheep red blood cells and reimmunized one week later. Five‐week‐old birds were sacrificed during a 24 h period every 4 h. The existence of the diurnal rhythm was evaluated by cosinor analysis. The diurnal rhythm of total white blood cells and serum agglutinins was more dependent on the time of melatonin injections than on the hormone used. The effect of melatonin injections on the level of immune parameters examined was also dependent on the time of sample collection. Results obtained indicate the participation of pineal gland in the regulation of the diurnal rhythm of the examined indices of avian immune system function that exhibit diurnal changes in sensitivity to exogenous melatonin.
Effects of melatonin on the cell cycle kinetics and “estrogen‐rescue” of MCF‐7 human breast cancer cells in culture
Authors: Cos Samuel , Blask David E. , Lemus‐Wilson Athena , Hill Anna B.
Published: February 2007

Cos S, Blask DE, Lemus‐Wilson A, Hill AB. Effects of melatonin on the cell cycle kinetics and “estrogen‐rescue of MCF‐7 human breast cancer cells in culture. J Pineal Res 1991:10:3642.

Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen‐responsive MCF‐7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G1 phase of the cell cycle, thus causing a transition delay into the S phase. In order to further verify this hypothesis we tested the ability of estradiol to “rescue” MCF‐7 cells from melatonin inhibition, and the potential of this indoleamine to block the ability of estradiol to rescue the cells from tamoxifen inhibition. Following five days of incubation, melatonin (10‐9M) increased the fraction of cells in G1 of the cell cycle while simultaneously causing a 50% reduction in the proportion of cells in S phase. The antiproliferative effect of melatonin (11‐5M) was prevented by the simultaneous treatment of the cells with estradiol (10‐8M) in clonogenic soft agar culture, or reversed by the addition of estradiol to cells previously incubated with and inhibited by melatonin (10‐9M) in monolayer culture. Additionally, melatonin blocked the estrogen‐rescue of tamoxifen‐inhibited cells in both types of culture systems. These results support the hypothesis that the antiproliferative effect of melatonin, like tamoxifen, is cell cycle specific by causing a G1‐S transition delay. These results also indicate an important interaction of melatonin with estrogen‐mediated mechanisms of MCF‐7 cell proliferation.
Chronic administration of sublethal doses of carbaryl increases pineal N‐acetyltransferase and hydroxyindole‐O‐methyltransferase activities and serum melatonin levels
Authors: Attia Ahmed M. , Reiter Russel J. , Withyachumnarnkul Boonsirm , Mostafa Mostafa H. , Soliman Salah A. , El‐sebae Abdel‐Khalek H.
Published: February 2007

Attia AM, Reiter RJ, Withyachumnarnkul B, Mostafa MH, Soliman SA, El‐sebae A.‐K.H. Chronic administration of sublethal doses of carbaryl increases pineal N‐acetyltransferase and hydroxy‐0‐ rnethyltransferase activities and serum melatonin levels. J Pineal Res 1 99 1 1 0149‐54.

The purpose of this study was to examine the effects of chronic administration of sublethal doses of carbaryl on pineal melatonin synthesis. N‐methyl 1‐naphthylcarbamate (carbaryl) (8.33 mg/kg B.W. daily) was administered orally to adult male albino rats for 6 successive days. Nocturnal (0100) N‐acetyltransferase and hydroxyindole‐0‐methyltransferase activities were increased (roughly 75% and 60%, respectively) by carbaryl administration; likewise, carbaryl augmented serum melatonin levels at 2300. Pineal tryptophan, 5‐hydroxytryptophan, serotonin, and 5‐hydroxindole acetic acid levels were unaffected at all three time points. The results indicate that the carbamate pesticide, i.e., carbaryl, modifies pineal melatonin synthesis in vivo.
Insulin release from isolated mouse islets in vitro: No effect of physiological levels of melatonin or arginine vasotocin
Authors: Frankel Barbara J. , Strandberg Malin J.
Published: February 2007

Abstract: Some data in the literature suggest that heightened activity of the pineal gland may be diabetogenic. The onset of insulin‐dependent diabetes mellitus is highest during the winter months and at puberty when melatonin levels are also greatest. To study the direct effects of pineal hormones on insulin release, hand‐dissected ob/ob‐mouse islets of Langerhans were incubated in vitro with melatonin (1 nmol/1 to 100 μmol/1) or arginine vasotocin (1 pmo1/1 to 10 μmol/1) and D‐glucose (3 or 20 mmol/1 for 1 hr. Melatonin did not affect basal or glucose‐stimulated insulin release. Arginine vasotocin (AVT) did not affect basal insulin release, but at presumably pharmacological levels (1 and 10 μmol/1) the peptide significantly increased glucose‐stimulated insulin release. We conclude that melatonin and AVT at physiological concentrations have no direct effect on islet insulin release, and that any diabetogenic effect of the pineal gland must occur via suppression of insulin action or via production of a metabolite or hormone that suppresses insulin release.
Effects of different doses and durations of melatonin infusions on plasma melatonin concentrations in pinealectomized Syrian hamsters: Consequences at the level of sexual activity
Authors: Pitrosky B. , Masson‐Pevet M. , Kirsch R. , Vivien‐Roels B. , Canguilhem B. , Pévet P.
Published: February 2007

Abstract: The effect of different doses and durations of melatonin infusions on plasma melatonin concentrations has been studied in pinealectomized Syrian hamsters maintained under short photoperiod at either 7°C or 18°C. The effects of the infusions on plasma melatonin concentrations and on gonadal activity were compared. The results show that the minimal effective quantity of infused melatonin that induced gonadal atrophy was 40 ng/h at 7°C and 20 ng/h at 18°C. An infusion of 8 hr duration per day is necessary to inhibit sexual activity, while an infusion of 6 hr duration was ineffective. This finding suggests that the critical duration of melatonin infusion is between 6 and 8 hr. Despite the various doses of melatonin infused, plasma melatonin concentrations measured in the middle of the infusion period did not differ significantly from concentrations measured in intact animals. This finding suggests that the metabolism of infused melatonin increases as the dose of melatonin increases. Moreover, the different physiological effects observed after the various melatonin infusions cannot be explained by variations in plasma melatonin concentrations.
Identification of serotonin 5HT2 receptors in bovine pineal gland
Authors: Govitrapong P. , Prapapanich V. , Ebadi M.
Published: February 2007

Abstract: The concentration of serotonin in the pineal gland is extremely high, which prompted speculation that in addition to serving as a precursor of melatonin, serotonin may have an independent function of its own. By using [3H]‐spiperone as a ligand, and ketanserine as a selective serotonin 5HT2 receptor antagonist, we have identified 5HT2 receptor in the bovine pineal gland, revealing a single population of binding sites with a dissociation equilibrium constant (Kd) value of 1.26 ± 0.41 nM and a receptor density (Bmax) value of 193 ± 38.85 fmol/mg protein. In displacement experiments, the concentrations of the drugs required to inhibit 50% of the specific binding of [3H]‐spiperone in descending order of potency were methysergide > ritanserin > pirenperone > pipamperone > ketanserin > cyproheptadine > M‐trifluoromethylphenyl‐piperazine > prazosin > 5‐methoxy‐N‐N‐dimethyltryptamine hydrogen oxalate > 1‐(3‐chlorophenol) piperazine > serotonin. In the rat pineal gland, [3H]‐spiperone revealed a low affinity serotonin binding site with a Kd value of 25.77 ± 10.7 nM and a Bmax value of 1244 ± 472 fmol/mg protein. The results of these studies are interpreted to indicate that the bovine pineal gland possess serotonin 5HT2 receptor. However, the rat pineal gland possess a serotoninergic binding site of unknown nature.
Presynaptic effects of melatonin on norepinephrine release and uptake in rat pineal gland
Authors: Chuluyan Héctor E. , Rosenstein Ruth E. , Chang Su Min , Gálvez María M. , Cardinali Daniel P.
Published: February 2007

Abstract: The effect of melatonin injection on norepinephrine (NE) turnover rate in rat pineal gland was estimated from the decline of tissue NE levels after the injection of the tyrosine hydroxylase inhibitor α‐methyl‐p‐tyrosine. The administration of a single injection of 300 μg/Kg of melatonin at the beginning of the scotophase induced, 3 hr later, a significant decrease of pineal NE turnover. The possible direct effect of melatonin on pineal NE release was examined in vitro. Exposure of rat pineal expiants previously loaded with 3H‐NE to 10−8‐10−6 M melatonin decreased significantly 3H‐NE release triggered by 60 mM K+. This activity of melatonin was revealed only in pineals excised at night (0000 and 0400, i.e., at the fourth or eighth hours of darkness) and not in those excised in the middle (1400) or late light phase of the daily photoperiod (2000). Melatonin did not modify the spontaneous pineal 3H‐NE efflux. Melatonin decreased 3H‐NE uptake at a low NE concentration (0.5 μM) in a dose‐dependent manner (IC50≡ 10−10 M). A kinetic analysis of the pineal NE uptake process indicated that melatonin augmented both Vmax and Km of transmitter uptake. These results suggest that endogenously released melatonin may be a regultory signal for rat pineal sympathetic synapses.
Purinergic receptors have no major role in control of the circadian rhythm in rate of thymidine incorporation by cultured chick pineal glands
Authors: Wainwright S.D. , Wainwright Lillian K.
Published: February 2007

Abstract: We have examined the effects of some analogues of adenosine upon the circadian rhythm in rate of thymidine incorporation by cultured chick pineal glands. Incorporation in the early period of the photoperiod on day 2 of culture was slightly inhibited by the adenosine analogue N‐ethylcarboxamido‐adenosine, but this effect was not countered by the antagonist 8‐phenyl‐theophylline. Thymidine incorporation was inhibited when glands were continuously exposed to the adenosine transport inhibitor nitrobenzyl‐thioinosine, but ongoing incorporation was not inhibited by addition of this agent. Removal of adenosine and deoxyadenosine supplements from the medium, with or without further addition of adenosine deaminase, had no appreciable effects upon thymidine incorporation. We conclude that adenosine and analogues probably play no role in regulation of the rhythm in rate of thymidine incorporation.
Pineal influence on the diurnal rhythm of nonspecific immunity indices in chickens
Authors: Rosołowska‐Huszcz Danuta , Tnaela Mary‐Jane , Jagura Monika , Stȩpień Diana , Skwarło‐Sońta Krystyna
Published: February 2007

Abstract: The effect of pinealectpmy and melatonin injections on the diurnal rhythms of serum lysozyme and blood granulocytes was examined in White Leghorn cockerels kept from time of hatching for 5 weeks in L:D 12:12 conditions and immunized twice with sheep red blood cells (SRBC). Pinealectomy or sham‐operation was made during first week of life. Pinealectomized chickens were injected daily with a melatonin dosage increased over 4 consecutive weeks (the dosage was 10, 13, 16, and 20 ng per bird daily during the 4 weeks, respectively; MEL I) at the beginning of darkness. The same treatment was performed on chickens with an intact pineal gland using additional melatonin doses increased 10 times (MEL II) and 500 times (MEL III). Intact chickens were also injected with MEL II and MEL III 4 hr before the end of light. Control birds received equivalent injections of vehicle. Five‐week‐old chickens were sacrificed during a 24‐hr period every 4 hr. The existence of diurnal rhythm was evaluated by cosinor analysis. Pinealectomy shifted the acrophase of the diurnal rhythm of granulocytes and abolished that of serum lysozyme. Both rhythms were restored in pinealectomized chickens by MEL I but not by vehicle injections. The same melatonin dose was unable to change the granulocyte rhythm but delayed the acrophase of that of serum lysozyme in chickens with an intact pineal gland. Two higher melatonin doses influenced the diurnal rhythm of granulocytes as a function of dose and time of administration. The rhythm of serum lysozyme was dependent only on the time of injection. The pineal gland seems to control, via its hormone melatonin, the diurnal rhythm of nonspecific immunity in chickens.
Melatonin‐induced enhancement of antibody‐dependent cellular cytotoxicity
Authors: Giordano Mirta , Palermo Marina S.
Published: February 2007

Abstract: Antibody‐dependent cellular cytotoxicity (ADCC) is a lytic mechanism in which a specific antibody acts cooperatively with leukocytic effector cells to induce target cell lysis. In this paper, the effect of exogenous melatonin on ADCC was examined. It was found that two evening intravenous injections of melatonin (1 mg/kg b.w.) was sufficient to enhance the capacity of splenocytes to mediate ADCC. This augmented activity returned to normal levels by day 6. Moreover, the opioid antagonist, naloxone, was unable to inhibit the ADCC enhancement, suggesting that melatonin did not operate through a naloxone‐sensitive opiatergic mechanism. These results further support the modulatory action of melatonin on immune responses.
Melatonin, a suppressor of spontaneous murine mammary tumors
Authors: Subramanian Asha , Kothari Lalita
Published: February 2007

Abstract: The effect of prolonged, oral melatonin treatment on spontaneous mammary tumor development in female C3H/Jax mice was studied. Melatonin was administered at a dose of 25 μg/mouse/day from 21 to 44 days of age and 50 μg/mouse/day from day 45 onwards. By the age of 12 months, 62.5% of control animals developed tumors as opposed to 23.1% in the melatonin treated group (P < 0.02). In both control and treated mice, the thoracic pairs of mammary glands were obviously more susceptible to spontaneous mammary tumor development, as at least 50% of the total tumors developed in this region. Reduction in submaxillary and pituitary gland weights of treated animals was observed at necropsy (P < 0.001). Decreased serum 17‐β‐estradiol (E2) levels in melatonin treated mice (P < 0.05) and a marked reduction in [3H]thymidine incorporation into DNA of melatonin‐treated mammary glands (P < 0.02) positively correlated with the sparse mammary gland development seen in these mice. These observations indicate that at the given dose level, melatonin modulates the degree of development of the mammary epithelium, subsequently reducing spontaneous mammary tumor incidence in these high risk mice.
Pineal and retinal protein kinase C isoenzymes: Cooperative activation by calcium and zinc metallothionein
Authors: Ou C.Z. , Ebadi M.
Published: February 2007

Abstract: Protein kinase C and its family of multiple subspecies play pivotal roles in cell‐surface mediated signal transduction. For example, in the process of synthesizing melatonin, the activation of α1‐adrenergic receptor sites in the pineal gland causes translocation of protein kinase C, which in turn enhances the β‐adrenergic‐activated accumulation of both cyclic AMP and cyclic GMP. In the retina, protein kinase C phosphorylates rhodopsin and hence is involved in visual transduction. The activation of protein kinase C depends on the presence of phospholipid and Ca++. In this communication, we report that the bovine pineal gland and retina possess unique protein kinase C isoenzymes that are distinct from those seen in the rat brain. Furthermore, in retinoblastoma cells in culture, protein kinase C is stimulated by a cooperative interaction between calcium and zinc. Moreover, the subcellular regions of retina that exhibit the highest activity of protein kinase C also possess the highest concentration of zinc. In view of the fact that the bovine pineal gland and retina continually synthesize metallothionein and other low molecular weight zinc binding proteins, we propose that zinc and metallothionein participate in signal transduction in the retina and pineal gland. The action of metallothionein, a zinc binding protein, in activating protein kinase C is opposite to that of calcium binding protein, which is a potent inhibitor of protein kinase C.
Vasoactive intestinal peptide stimulates N‐acetyltransferase and hydroxyindole‐O‐methyltransferase activities and melatonin production in cultured rat but not in Syrian hamster pineal glands
Authors: Moujir Fatima , Richardson Bruce A. , Yaga Ken , Reiter Russel J.
Published: February 2007

Abstract: The purpose of this study was to compare the responses of the Syrian hamster and rat pineal glands in organ culture to vasoactive intestinal peptide (VIP). The endpoints in these studies were the activities of pineal N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT), as well as pineal and medium melatonin levels. When rat pineal glands were incubated with either VIP (1 μM) or isoproterenol (1 μM), a β‐adrenergic agonist, a significant increase in NAT and HIOMT activities and melatonin levels were observed within 3 hr. Conversely, during the day, VIP (1 μM) was ineffective in stimulating these parameters in hamster pineal gland after incubation times of either 2, 4, 6, or 8 hr. In another experiment, hamster pineal glands were collected from animals killed in the late dark period (after 30 min light exposure). In these glands, isoproterenol promoted NAT activity and melatonin production; however, VIP was ineffective in stimulating either NAT or HIOMT activities; likewise, VIP had no stimulatory effect on pineal melatonin levels at night. Finally, when hamster pineal glands at night were incubated with either 0, 10 nM, 100 nM, 10 μM, or 100 μM VIP, no changes in any parameter of melatonin synthesis were measured. The results indicate that the hamster pineal gland, unlike that of the rat, may not respond to VIP with an increased melatonin production.
Peripheral vision suppression of melatonin
Authors: Adler Joshua S. , Kripke Daniel F. , Loving Richard T. , Berga Sarah L.
Published: February 2007

Abstract: The suppression of melatonin by bright light is probably mediated by the suprachiasmatic nucleus (SCN) in humans. In animals, SCN cells have broad visual receptive fields, suggesting that peripheral bright light could be effective for melatonin suppression. Twelve healthy subjects were subjected to 1000 lux illumination for 2 hr from 0100 to 0300 on two occasions: once lighting the central visual field 5° from the center of gaze and once lighting the peripheral visual field 60° lateral to the direction of gaze. Six subjects were observed on a third occasion in dim light. The three conditions differed significantly, with less melatonin secreted in 1000 lux, but melatonin levels with central and peripheral illumination did not differ. This suggests that phototherapy using bright light in the visual periphery may be effective.
Seasonal profiles of melatonin in adult rams
Authors: Sheikheldin Mirghani A. , Howland Borden E. , Palmer W. Martyn
Published: February 2007

Abstract: The objective of this study was to investigate the seasonal changes in melatonin profiles based on frequently collected samples in adult rams maintained under simulated natural photoperiod. In a group of six rams, the seasonal changes of melatonin were characterized in samples collected at 10‐min intervals for an equal period before and after the median of the scotophase during the spring (March) and the autumn (September) equinoxes, and also during the summer (June) and the winter (December) solstices. In an additional two rams, the rapid changes in melatonin concentrations were investigated in samples drawn at 2‐min intervals for a 2‐hr period before and after the median of the scotophase, but only during the summer and the winter solstices. The results show that in adult rams there is a distinct seasonal variation in the nightly rise of melatonin (P < 0.01). Mean concentrations in June and September were higher than in March or December (P < 0.05). There was no difference between the means in June or September. However, the means in March were lower than in December (P < 0.05). Rapid changes in melatonin concentrations occurred in samples collected either at 10‐min or 2‐min intervals. In rams sampled at 2‐min intervals, mean melatonin values in June were also higher than in December (P < 0.01). The results suggest that there are distinct seasonal changes in melatonin concentrations in the ram and that rapid changes in melatonin concentrations reflect pulsatile secretion.
Interaction of melatonin with human lymphocytes: Evidence for binding sites coupled to potentiation of cyclic AMP stimulated by vasoactive intestinal peptide and activation of cyclic GMP
Authors: Lopez‐Gonzalez Miguel A. , Calvo Juan R. , Osuna Carmen , Guerrero Juan M.
Published: February 2007

Abstract: Melatonin binding sites were characterized in human blood lymphocytes. The specific binding 2‐[125I]iodomelatonin ([125I]MEL) to human lymphocytes was dependent on time and temperature, stability, saturation, and reversibility. Moreover, guanine nucleotides decreased the specific binding of [125I]MEL to crude membranes of human lymphocytes, suggesting the coupling of these binding sites to a guanosine nucleotide binding regulatory protein(s). In competition studies, the specific binding of [125I]MEL to lymphocytes was inhibited by increasing concentrations of native melatonin. Scatchard analysis showed that data were compatible with the existence of two classes of binding sites: a high‐affinity site with a Kd of 5.20 ± 0.79 nM and a binding capacity of 50.6 ± 11.0 fmol/107 cells, and a low‐affinity site with a Kd of 208.5 ± 50.2 nM and a binding capacity of 2691 ± 265 fmol/107 cells. However, concentration‐dependent binding of [125I]MEL to lymphocytes was saturable and resulted in a linear Scatchard plot, suggesting binding to a single class of binding sites. The Kd for the single site was 1.02 ± 0.34 nM with a binding capacity of 10.1 ± 1.6 fmol/107 cells. Their affinities closely correlated with the production of cyclic nucleotides, suggesting a physiological role for the melatonin binding sites. Thus, melatonin potentiated the effect of vasoactive intestinal peptide (VIP) on cyclic AMP production (ED50= 1.9 nM) and stimulated cyclic GMP accumulation (ED50= 125 nM). Results demonstrate the existence of two binding sites for [125I]MEL in human blood lymphocytes, with a high‐affinity binding site coupled to the potentiation of the effect of VIP on cyclic AMP production and a low‐affinity binding site coupled to activation of cyclic GMP production.
Circadian rhythms of plasma melatonin in the ruin lizard Podarcis sicula: Effects of pinealectomy
Authors: Foa Augusto , Janik Daniel , Minutini Lucia
Published: February 2007

Abstract: Plasma melatonin was measured in lizards (Podarcis sicula) at six different times of day under conditions of constant temperature and darkness. Intact animals showed a circadian rhythm of melatonin with a peak in the subjective night of 207 pg/ml (median) and a trough during the subjective day that was below the minimum detection level of the assay (50 pg/ml). Pinealectomy abolished the circadian rhythm of plasma melatonin; median levels were near or below the minimum detection level at all times sampled. The data suggest that the pineal is the only source of rhythmic blood‐borne melatonin in Podarcis sicula, and are consistent with the hypothesis that changes in the free‐running period of the locomotor rhythm induced by pinealectomy in this species are due to withdrawal of rhythmic melatonin from the blood.