bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland
Authors: Noteborn H.P.J.M. , Balen P.P. van , Gugten A.A. van der , Hart I.C. , Ebels I. , Salemink C.A.
Published: February 2007

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL‐like ir‐material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH‐like immunoreactivity. Gel chromatography of the GH‐like immunoreactivity (Sephadex G‐100) indicated the presence of several GH‐like fragments ranging in the Mr range of 7,000 to 55,000. Analyses of the PRL‐like ir‐material found in pineal tissue on HPLC using a TSK 545‐DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir‐peak from the TSK 545‐DEAE column. The PRL‐like ir‐material inhibited the binding of [125I]ovine PRL‐S14 to anti‐ovine PRL antibodies without showing an affinity for binding to anti‐rat PRL or anti‐bovine GH antibodies. Scatchard analysis of the binding of pineal PRL‐like ir‐material and pituitary ovine PRL‐S14 to liver membranes from day‐20 pregnant rats revealed similar affinity constants (Ka of 4.7 ± 0.2 × 109 M‐1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL‐like ir‐material, an effect known to be specific for lactogenic hormones. The pineal PRL‐like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of Mr 24,000. The functional status of PRL‐and GH‐like ir‐material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.
Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland
Authors: Berthoud Viviana M. , Sáez Juan C.
Published: February 2007

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.
Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one‐week‐and two‐month‐old rats: Planimetric and densitometric investigations
Authors: Wicht Helmut , Korf Horst‐Werner , Schaad Nicolas C.
Published: February 2007

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one‐week‐and two‐month‐old rats, attached to synthetic peptide‐coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one‐week‐old animals were smaller than the cells from the two‐month‐old animals. Immunocytochemical demonstration of S‐antigen, a pinealocyte‐specific marker, showed that the majority of the cells from two‐month‐old animals were intensely or moderately labelled. Pinealocytes from one‐week‐old animals were less S‐antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)‐immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S‐antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one‐week‐old to two‐month‐old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S‐antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S‐antigen immunoreacti vitv.
Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis
Authors: Poeggeler Burkhard , Reiter Russel J. , Tan Dun‐Xian , Chen Li‐Dun , Manchester Lucien C.
Published: February 2007

Abstract: Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on‐site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non‐enzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally related tryptophan metabolites are evolutionary conservative molecules principally involved in the prevention of oxidative stress in organisms as different as algae and rats. The rate of aging and the time of onset of age‐related diseases in rodents can be retarded by the administration of melatonin or treatments that preserve the endogenous rhythm of melatonin formation. The release of excitatory amino acids such as glutamate enhances endogenous hydroxyl radical formation. The activation of central excitatory amino acid receptors suppress melatonin synthesis and is therefore accompanied by a reduced detoxification rate of hydroxyl radicals. Aged animals and humans are melatonin‐deficient and more sensitive to oxidative stress. Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of melatonin biosynthesis such as magnesium may finally lead to novel therapeutic approaches for the prevention of degeneration and dysdifferentiation associated with diseases related to premature aging.
Hydroxyindole‐O‐methyltransferase activity in ocular and brain structures of rabbit and hen
Authors: Nowak Jerzy Z. , Szymańska Bożena , Zawilska Jolanta B. , Białek Bogusław
Published: February 2007

Abstract: Relative activities of hydroxyindole‐O‐methyltransferase (HIOMT) of some brain and ocular structures of the rabbit and hen were analyzed using different 5‐hydroxyindoles, i.e., N‐acetylserotonin (NAS), 5‐hydroxytryptophol (HTOL), 5‐hydroxytryptophan (HTP), 5‐hydroxytryptamine (HT), and 5‐hydroxy‐3‐indoleacetic acid (HIAA), as enzyme substrates. Pineal glands of both species, as well as hen retina, are capable of producing, to varying degrees, melatonin, 5‐methoxytryptophol, and 5‐methoxytryptamine. Hen choroid and iris‐ciliary body O‐methylated NAS and HTOL, whereas rabbit choroid and, to a much lesser extent, hypothalamus and cerebral cortex all O‐methylated only NAS. No measurable HIOMT activity was found in hen brain. NAS was a preferred substrate for HIOMT in the hen tissues, whereas in the rabbit pineal gland NAS and HTOL were equally good substrates for HIOMT. Other tested 5‐hydroxyindoles, i.e., HTP, HT, and HIAA, were poor methyl acceptors. Of the tissues examined, the highest HIOMT activity was found in the hen pineal gland, followed by the rabbit pineal gland and hen retina. No significant differences between day and nighttime enzyme activities were observed in the pineal gland and retina of either species. The data suggest that in vertebrates some nervous and ocular tissues possess the potential to produce 5‐methoxyindole compounds; however, the HIOMT‐catalyzed process shows remarkable substrate, tissue‐and species‐dependent variations.
Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children
Authors: Molina‐Carballo A. , Acuña‐Castroviejo D. , Rodriguez‐Cabezas T. , Muñoz‐Hoyos A.
Published: February 2007

Molina‐Carballo A, Acuna‐Castroviejo D, Rodriguez‐Cabezas T, Munoz‐Hoyos A. Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children. J. Pineal Res. 1994: 16: 1–9.

Plasma melatonin was measured in 118 infants and children (39 controls, 28 with epileptic convulsions, and 51 with febrile convulsions). The control group displayed a typical circadian rhythm, with melatonin peaking between 0200 and 0400. This normal daily variation significantly changed in the epileptic group, which showed a characteristic phase‐advance, with the nocturnal melatonin peak appearing between 2400 and 0200. Febrile convulsions were associated with the disappearance of the normal circadian rhythm of melatonin, which was replaced by melatonin bursts throughout the light: dark cycle. In both febrile and epileptic children, melatonin levels were significantly increased in comparison with normal children.
Detection and quantification of melatonin in a dinoflagellate, Gonyaulax polyedra: Solutions to the problem of methoxyindole destruction in non‐vertebrate material
Authors: Poeggeler Burkhard , Hardeland Rüdiger
Published: February 2007

Poeggeler B, Hardeland R. Detection and quantification of melatonin in a dinoflagellate, Gonyaulax polyedra: Solutions to the problem of methoxyindole destruction in non‐vertebrate material. J. Pineal Res. 1994: 17: 1–10.

Preservative procedures are described for the extraction and quantification of melatonin in cell material from the dinoflagellate Gonyaulax polyedra, an organism in which this indoleamine is rapidly degraded due to interaction with free oxygen radicals and photooxida‐tion. Cells were shock‐frozen in liquid nitrogen and pulverized. Various extraction methods were applied to the powder, and rates of recovery were compared. For the determination of melatonin by high performance liquid chromatography (HPLC), extractions with acetone or perchloric acid were more suitable than the use of other solvents. For purposes of radioimmunoassay (RIA), extraction with acetone gave the best results. Several other inorganic solvents, which are often applied in melatonin research, such as chloroform, dichloromethane, and diethyl ether, led to considerable losses of the indoleamine. The procedures developed for HPLC with either electrochemical or fluorescence detection also allow the quantification of other indolic compounds, in particular, tryptophan and 5‐methoxytryptamine. The methods described may be of value in the further search for melatonin and related indoleamines in non‐vertebrate material, especially, from unicells, multicellular plants, and invertebrates.
Effect of two weeks of continuous light on the development of the circadian melatonin rhythm in newborn lambs
Authors: Fielke S. L. , Young I. R. , Walker D. W. , McMillen I. C.
Published: February 2007

Fielke SI, Young IR, Walker DW, McMillen IC. Effect of two weeks of continuous light on the development of the circadian melatonin rhythm in newborn lambs. J. Pineal Res. 1994; 17: 118–122

We have investigated the effect of exposure of newborn lambs to continuous light during the first 2 weeks after birth on the subsequent development of the phase and amplitude of the plasma melatonin rhythm during the next 8 weeks. During the first 2 weeks after birth, the mean plasma melatonin concentrations were significantly lower (P < 0. 001) in lambs exposed to continuous light (58 ± 15 pmol/1, n = 7) than in lambs exposed to LD 12: 12 (i. e., “normal” lighting: 189 ± 38 pmol/1, n = 9). Between 3 and 4 weeks of age, plasma melatonin concentrations during the daily light and dark periods were also significantly lower in the lambs exposed to continuous light during the first 2 weeks after birth. There was no effect of time of day on plasma melatonin in either group of lambs during the first 2 weeks after birth but between 3 and 10 weeks of age there was a significant (P < 0. 001) effect of light and dark and time of day on plasma melatonin concentrations which was the same in both groups of lambs. Plasma melatonin concentrations were higher in the dark period than in the light period and between 2100 and 0700 than between 0900 and 1700 at all ages after week 2. We have therefore demonstrated that exposure of the lamb to 2 weeks of continuous light after birth results in a suppression of melatonin secretion that extends beyond the end of the exposure to continuous light.
Modulation of melatonin secretion by acetyl‐L‐carnitine in adult and old rats
Authors: Esposti D. , Mariani M. , Demartini G. , Lucini V. , Fraschini F. , Mancia M.
Published: February 2007

Esposti D, Mariani M, Demartini G, Lucini V, Fraschini F, Mancia M. Modulation of melatonin secretion by acetyl‐L‐carnitine in adult and old rats. J. Pineal Res. 1994; 17: 132–136.

Abstract; Modification of melatonin synthesis and release by acetyl‐L‐carnitine (ALC) was studied in adult (2 month old) and old (24‐month‐old) male Sprague Dawley rats. When ALC was injected at 1500 into adult rats at doses of 10, 30, or 90 mg/kg, there was a remarkable increase in their pineal and serum melatonin 1 hr later. However, using the same experimental protocol acute ALC administration in old rats did not modify pineal and serum melatonin levels. ALC administered in the same dose range induced a significant increase in pineal and serum melatonin in adult rats treated at 0100 h following exposure of 30 min to bright, white light to suppress endogenous melatonin. In the same conditions, in old rats, only the higher dose (90 mg/kg) caused any noteworthy increase in melatonin pineal content while lower doses were ineffective both on serum and pineal melatonin levels. It is known that ALC affects fatty acid transport in the cells, modulates Co A, modifies neuronal transmission and reduces lipofuscin accumulation which is related to lipid per oxidation. The action of ALC on melatonin synthesis could be the result of a modulation of the neuronal transmission related to circadian pineal endocrine activity. Moreover, since both ALC and melatonin exert remarkable scavenger activity, it is possible to suppose that ALC effects in reversing certain aging processing may be due to its ability to promote melatonin production.
Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography‐mass spectrometry
Authors: Dubbels R. , Reiter R.J. , Klenke E. , Goebel A. , Schnakenberg E. , Ehlers C. , Schiwara H.W. , Schloot W.
Published: February 2007

Abstract: Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by‐products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage.
Prenatal alcohol exposure and pineal response to isoproterenol, vasoactive intestinal polypeptide, and desmethvlimipramine
Authors: Yuwiler A. , Taylor A.N.
Published: February 2007

Abstract: Pineals from neonatal rats born to alcohol‐fed mothers had lower unstimulated serotonin‐N‐acetyltransferase activity (NAT) and responded less to isoproterenol, vasoactive intestinal polypeptide, or desmethylimipramine challenge than did pineals from pups born to normal or pair‐fed mothers. Group differences disappeared after the first week of life. Reduced NAT activity is coincident with elevated glucocorticoids in these pups. In contrast to these effects of chronic in utero ethanol exposure, acute ethanol addition to normal adult pineals in organ culture enhanced ISO but not VIP stimulation of NAT activity. The results suggest that the neonatal pineal is more affected by ethanol‐induced activation of the adrenocortical axis during gestation than by the direct effect of ethanol on membrane fluidity.
Daytime dark exposure increases pineal melatonin in rat pups
Authors: Laakso Maija‐Liisa , Hätönen Taina , Alila Aino
Published: February 2007

Abstract: Photic regulation of the pineal melatonin synthesis was studied in 3‐ to 21‐day‐old rat pups by exposing the animals to light at night (30–40 min) or to darkness during the day (30–240 min). The pineal melatonin contents were measured by radioimmunoassay. A significant day/night difference in the melatonin content and the nocturnal light‐induced decrease were not found until second postnatal week. A novel finding was that at the age of 13–17 days a daytime dark exposure elevated the pineal melatonin content; it was twofold as compared with the normal daytime level and about half of the nocturnal peak level. In 21‐day‐old rats the response had disappeared, while the nocturnal suppression by light persisted. The dark‐induced increase of the melatonin synthesis was independent of the opening of the eyelids which occurs in pups at the age of two weeks, but it was greater in maternally isolated than non‐isolated pups. The results suggest that one component of the circadian regulatory system matures at the end of the third postnatal week. This mechanism inhibits the elevation of the melatonin synthesis by darkness during the daytime.
Neurotrophic effects of the pineal gland: Role of non‐neuronal cells in co‐cultures of the pineal gland and superior cervical ganglia
Authors: McNulty John A. , Tsai Shin‐Yen , Fox Linda M. , Madsen Torsten M. , Silberman Simon , Tonder Niels
Published: February 2007

Abstract: The pineal gland (PG) is a source of several trophic factors. In this study, PG and superior cervical ganglia (SCG) from Sprague‐Dawley neonates (1‐day‐old) were co‐cultured to test the hypothesis that endogenous release of PG NGF (or an NGF‐like cytokine) is sufficient to promote survival of SCG neurons. Neuronal density of SCG neurons was significantly enhanced when co‐cultured with PG for 7 days compared to SCG cultured alone. SCG survival and neurite formation in PG co‐cultures was less than in SCG treated with exogenous NGF (100 ng/ml). The neurotrophic effect of PG co‐cultures was abolished when 1% anti‐NGF was added to the medium. Co‐cultures of SCG neurons with established 7‐day PG cultures induced extensive SCG neurite formation within 24 hr compared to SCG co‐cultured with 1‐day PG cultures. This suggests that PG neurotrophic effects are due to PG non‐neuronal cells (nnc) that proliferate to confluency by 7 days in culture. S‐antigen‐positive pinealocytes did not proliferate in culture. There was decreased SCG survival when neurons were seeded onto PG cultures that had been previously killed by drying, which suggests that the neurotrophic effects of nnc are not substrate‐dependent. Immunocytochemical characterization of PG nnc revealed a heterogenous mixture of astrocytes, macrophage/ microglia, and fibroblasts. These findings support the hypothesis that NGF is actively secreted by PG and that nnc are the principal source of this neurotophin.
Melatonin reduces H2O2‐induced lipid peroxidation in homogenates of different rat brain regions
Authors: Sewerynek Ewa , Melchiorri Daniela , Ortiz Genaro G. , Poeggeler Burkhard , Reiter Russel J.
Published: February 2007

Abstract: The ability of melatonin to modify H2O2‐induced lipid peroxidation in brain homogenates was determined. The concentrations of brain malonaldehyde (MDA) and 4‐hydroxyalkenals (4‐HDA) were assayed as an index of induced membrane oxidative damage. Homogenates from five different regions of the brain (cerebral cortex, cerebellum, hippocampus, hypothalamus, and corpus striatum) derived from two different strains of rats, Sprague‐Dawley and Wistar, were incubated with either H2O2 (5 mM) alone or H2O2 together with melatonin at increasing concentrations ranging from 0.1 to 4 mM. The basal level of lipid peroxidation was strain‐dependent and about 100% higher in homogenates from the brain of Wistar rats than those measured in Sprague‐Dawley rats. MDA + 4‐HDA levels increased after H2O2 treatment in homogenates obtained from each region of the brain in both rat strains but the sensitivity of the homogenates from Sprague‐Dawley rats was greater than that for the homogenates from Wistar rats (increases after H2O2from 45 to 165% compared 20 to 40% for Sprague‐Dawley and Wistar rats, respectively). Melatonin co‐treatment reduced H202‐induced lipid peroxidation in brain homogenates in a concentration‐dependent manner; the degree of protection against lipid peroxidation was similar in all brain regions.
Permeability of pure lipid bilayers to melatonin
Authors: Costa Ernane J.X. , Lopes Roberto Harzer , Lamy‐Freund M. Teresa
Published: February 2007

Abstract: Melatonin, the chief hormone of the pineal gland, has been reported to interact with a variety of different cells. This ubiquitously acting hormone has been found to interact with protein receptors both at the cell membrane and in the nucleus. Moreover, melatonin was recently shown to be a very potent hydroxyl radical scavenger. The present work focuses on the interaction of melatonin with pure lipid bilayers. It is shown that melatonin can cross multilamellar lipid vesicles, which are used here as model systems for the lipid phase of biological membranes. Thus, the data prove that melatonin can easily pass through the cell membrane and bath every part of the cell, as previously suggested in the literature. Melatonin lipid association constant was calculated based on the change of the hormone fluorescence intensity due to its penetration into the hydrophobic lipid phase. Though melatonin was recently shown to be highly soluble in aqueous media, its lipid association constant is rather high, indicating that the biological action of the hormone is likely to be at the membrane level, either via its interaction with membrane receptors, and/or as a lipoperoxidation radical scavenger.
Inhibitory effects of melatonin on testosterone but not on androstenedione production during winter in the vespertilionid bat, Scotophilus heathi
Authors: Singh Kavita , Krishna A.
Published: February 2007

Abstract: The possible effects of melatonin on testosterone and androstenedione production in vitro by testes of wild‐caught bats, Scotophilus heathi, during different reproductive phases were investigated. Bats were captured during reproductive quiescent (April‐August), recrudescent (September‐October), breeding (November‐February), and winter dormancy (late December‐January) phases. Testes were incubated in media‐199 for 2 h at 37°C with luteinizing hormone (LH) and with or without melatonin. Melatonin had no effect on LH‐induced testosterone (T) or androstenedione (A) production during the quiescent, recrudescent, and breeding phases. However, it significantly (P<0.05) suppressed LH‐induced T production but had no effect on A during winter dormancy. Testicular 17β‐hydroxy steroid dehydrogenase (17β‐HSD) activity was then measured in the testes from bats trapped during quiescence, breeding, and winter dormancy. Interestingly, melatonin along with LH caused suppression of 17β‐HSD activities (3.56 ± 0.03 unit/min/mg protein) when compared with levels of LH treated testes (7.10 ± 1.15 unit/min/mg protein) during winter dormancy, while it had no significant effect on 17β‐HSD activity during quiescence and breeding phases. These results suggest that in S. heathi, melatonin during winter dormancy suppresses LH‐induced T production by the testes via the suppression of 17β‐HSD activity. This may be the reason for the decline in testicular activity during winter dormancy.
Melatonin receptors in the rat brain and pituitary
Authors: Williams Lynda M. , Hannah Lisa T. , Hastings Michael H. , Maywood Elizabeth S.
Published: February 2007

Abstract: 2‐(125I)iodomelatonin binding has been mapped and characterized in the brain and pituitary of the male laboratory rat using quantitative in vitro autoradiography. Specific binding was defined as that completely displaced in the presence of 1 μM melatonin. In the brain high levels of binding were localized over the suprachiasmatic nucleus (SCN), the area postrema (AP), and the spinal tract of the trigeminal nerve (Sp5). Lower densities of binding were found over the medial preoptic area (MPA), the septohypothalamic nuclei (SHy), the anterior hypothalamic area (AHA), the nuclei of the lateral olfactory tract (LOT), the paraventricular (PV), anteroventral (AV) and intermediodorsal (IMD) nuclei of the thalamus, the medial region of the lateral habenular (Lhb), the nuclei of the stria medullaris (SM), the basolateral (BL) and medial (ME) amygdaloid nuclei, the ventromedial nuclei (VMH), the arcuate nuclei (Arc), the subiculum of the hippocampus (S) and the lateral mammillary nuclei (LM). High levels of binding were also present over the pars tuberalis of the pituitary (PT) and the anterior and posterior cerebral arteries (CA). In both neuronal and non‐neuronal areas, specific binding was time dependent and partially reversible in the presence of 1 μM melatonin. Binding was also saturable and of high affinity with dissociation constants (Kd) in the low picomolar range and was significantly inhibited in the presence of 104M guanosine 5′‐0‐(3‐thiotriphosphate) (GTPγS) and 150 mM NaCl in all regions examined, indicating the presence of high affinity G‐protein coupled melatonin receptors.
Reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites
Authors: Atsmon J. , Oaknin S. , Laudon M. , Laschiner S. , Gavish M. , Dagan Y. , Zisapel N.
Published: February 2007

Abstract: Recent reports indicate that benzodiazepines can suppress melatonin levels and that melatonin can increase brain benzodiazepine binding. We have studied the possibility of reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites. Daily injections (3 weeks) of diazepam markedly reduced 125I‐melatonin binding site density in the medulla‐pons but not cortex of male rats, whereas benzodiazepine binding was not significantly affected. Melatonin, administered via the drinking water, significantly enhanced benzodiazepine (3H‐RO 15‐1788) binding in the medulla‐pons and slightly reduced it in the cortex, but did not affect 125I‐melatonin binding. Diazepam and melatonin combination reversed the suppression by diazepam of 125I‐melatonin binding in the medulla‐pons and the suppression by melatonin of benzodiazepine (3H‐RO 15‐1788 and 3H‐flunitrazepam) binding in the cerebral cortex. These results indicate benzodiazepine‐mediated suppression of brain melatonin binding sites that can be abrogated by melatonin administration.
Acute and chronic effects of melatonin as an anticonvulsant in male gerbils
Authors: Champney Thomas H. , Hanneman William H. , Legare Marie E. , Appel Kevin
Published: February 2007

Abstract: Melatonin, a hormone produced in the pineal gland and released into the general circulation on a diurnal basis, has been implicated in many behavioral processes, where it has been shown to have anxiolytic, sedative, and anticonvulsant effects. Male gerbils (Meriones unguiculatus) injected daily with melatonin (25 μg, s.c.) exhibited a reduced seizure response to pentylenetetrazol (PTZ, 60 mg/kg, s.c). The present studies determined 1) whether melatonin's effect was related to the time of day that it was administered and 2) whether a single acute injection of melatonin at various doses could produce anticonvulsant activity. Gerbils provided with 13 weeks of daily melatonin injections (25 μg, s.c.) exhibited fewer convulsions after PTZ treatment irrespective of the time of day melatonin was injected. In addition, the melatonin‐treated gerbils had lower mortality rates (1/12) than the untreated or vehicle‐injected gerbils (5/12). On the other hand, single acute injections of melatonin (0.1–10 mg/kg, i.p.) produced no anticonvulsant activity. It appears that the anticonvulsant effects of melatonin occur only after the animals are chronically exposed to the indole. In addition, melatonin's anticonvulsant ability may utilize a different mechanism than those involved in its endocrine effects, since no diurnal difference in melatonin's anticonvulsant activity was observed.
Melatonin rhythms and pineal structure in a tropical bat, Anoura geoffroyi, that does not use photoperiod to regulate seasonal reproduction
Authors: Heideman R. D. , Bhatnagar K. R , Hilton F.K. , Bronson F.H.
Published: February 2007

Abstract: It has been hypothesized that pineal structure and function might differ between temperate zone and tropical species of mammals because of lower amplitudes of seasonal change in photoperiod and, in some areas, less seasonal climatic variation. Anoura geoffroyi produce a single offspring in November or December of each year on the Caribbean island of Trinidad, at 10°N latitude in the deep tropics. Previous work has shown that this population lacks reproductive responses to photoperiod, and must be enforcing seasonal breeding using a non‐photoperiodic cue. Anoura geoffroyi have a minute, thin, and rod‐like pineal gland. Throughout much of its length, the pineal courses irregularly within the ventrolateral wall of the great cerebral vein. This intimate relationship may have functional implications. Despite having a very small pineal gland, this species produced a nocturnal rise in serum melatonin. Serum melatonin levels in most individuals were below or near undetectable levels during the light period and rose to a peak averaging 100 pg/ml in the last third of the dark period. Our results indicate that, although the pineal gland of A. geoffroyi is extremely small, serum melatonin levels are comparable to those of other mammals.
6‐Hydroxymelatonin sulfate excretion in human puberty
Authors: Cavallo Anita , Dolan Lawrence M.
Published: February 2007

Abstract: We investigated the relationship of urinary excretion rate of 6‐hydroxymelatonin sulfate (SM), the main metabolite of melatonin, with pubertal development and determined the day to day variability of SM excretion. Healthy subjects 4–31 years old completed one or multiple timed overnight urine collections. SM excretion rate per body size was significantly higher in 99 prepubertal subjects (35.5 ± 2.3 ng/h/kg and 0.97 ± 0.06 μ/hr/m) than in 86 pubertal subjects (18.1 ± 1.1 ng/hr/kg and 0.61 ± 0.03 μg/hr/m2) or in 29 adults (15.0 ± 1.5 ng/hr/kg and 0.59 ± 0.06 μg/hr/ m2); no significant difference was present in pubertal stages 2 to 5. Among the prepubertal children, SM excretion rate in mid childhood was significantly higher than in late childhood. The variability of SM and creatinine excretion examined in 52 children, adolescents and adults with three or four collections was defined as the mean of the 52 coefficients of variation for the multiple measures in each subject. The variability of total nocturnal SM (25.9 ± 2.6%) was similar to that of total creatinine (21.7 ± 2.3%) and neither was significantly correlated with the variability in start time or duration of urine collection. The results suggest that, relative to body size, melatonin secretion rate is higher in mid childhood, decreases during late childhood, and remains stable from pubertal stage 2 to adulthood. The decline in melatonin secretion rate occurs during the developmental phase of disinhibition of the gonadotropin releasing hormone pulse generator. Hence, we infer that melatonin may be a suppressive factor of puberty during childhood. The substantial individual variability observed for SM excretion calls for caution in using single urine collections in longitudinal studies or in studies of drug responses.
Melatonin enhances Cortisol levels in aged women: Reversible by estrogens
Authors: Cagnacci A. , Soldani R. , Yen S.S.C.
Published: February 2007

Cagnacci A, Soldani R, Yen SSC. Melatonin enhances Cortisol levels in aged women: Reversible by estrogens. J. Pineal Res. 1997; 22:81–85. © Munksgaard, Copenhagen

The administration of melatonin increases Cortisol levels in postmenopausal women. Aging and hypoestrogenism are believed to impair the regulation of the hypothalamo‐pituitary‐adrenal axis and may participate in the determination of this altered response. In this study the implications of hypoestrogenism were tested. Seven postmenopausal women were studied. At 08.00 hr for 2 consecutive days, each woman received randomly and in a double blind fashion a pill of placebo or melatonin (100 mg). Serum melatonin and Cortisol levels were evaluated at 20 min intervals, for 48 hr. Measurements were performed in the same subjects both during no estrogen supplementation and at least two cycles of conjugated estrogens administration (0.625 mg/day). During estrogen supplementation, postmenopausal women showed slightly lower Cortisol levels at lunch and early night (20.00–01.00 hr). The onset of the nocturnal melatonin rise was not modified, but that of Cortisol was delayed of about 60 min (P<0.02). The administration of melatonin elicited a marked increase in daytime Cortisol levels in postmenopausal women (P<0.02), but this stimulus completely disappeared during estrogen administration. Mean nighttime (20.00–08.00 hr) Cortisol levels were not modified by daytime administration of melatonin. The present data reveal that in aged postmenopausal women, reversal of hypoestrogenism, resulting from supplemental estrogens, may improve the regulation of the hypothalamo‐pituitary‐adrenal axis.
Melatonin's antioxidant protection against δ‐aminolevulinic acid‐induced oxidative damage in rat cerebellum
Authors: Princ Fernando G. , Juknat Adela Ana , Maxit Andrea Grisel , Cardalda Carina , Battle Alcira
Published: February 2007

ABSTRACT: δ‐aminolevulinic acid (ALA) promotes the generation of reactive oxygen species (ROS). Accumulation of ALA, as occurs in acute intermittent porphyria (AIP), is a potential endogenous source of ROS, which can then exert oxidative damage to cell structures. In this work we investigated the role of pharmacological concentrations of melatonin on the deleterious effect of ALA and its effect on porphyrin biosynthesis. Rat cerebellum incubations were carried out with either ALA (1.0 mM) together with increasing concentrations of melatonin (0.1‐2.0 mM) or 2.0 mM melatonin together with varying ALA concentrations (0.05‐2.0 mM) for different times (1‐4 hr). ALA‐induced lipid peroxidation was significantly diminished by melatonin in a concentration‐dependent manner. In all conditions 2.0 mM melatonin restored malondialdehyde levels to control values. In incubations without ALA, melatonin markedly reduced (36‐40%) the basal levels of lipid peroxidation when compared with the corresponding controls. ALA uptake and porphyrin accumulation were increased 30% in incubations with 1.0–2.0 mM ALA for 4 hr in the presence of 2.0 mM melatonin, providing evidence for the involvement of ALA‐promoted ROS in the damage of enzymes related to porphyrin biosynthesis. These results are further support for the protective role of melatonin against oxidative damage induced by ALA; this protective action of melatonin is probably due to melatonin's antioxidant and free radical scavenger properties. The development of a new therapeutic approach for AIP patients employing melatonin alone or in combination with conventional treatments should be considered.
Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin
Authors: Lopes Cristiane , DeLyra Jorge Lacerda , Markus Regina Pekelmann , Mariano Mario
Published: February 2007

Lopes C, deLyra JL, Markus RP, Mariano M. Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin. J. Pineal Res. 1997; 23:72–78. © Munksgaard, Copenhagen

Biological rhythms are detected in a variety of physiological and pathological conditions in man and animals, such as rheumatoid arthritis and asthma. Here we describe a circadian rhythm in experimental infectious and non‐infectious granuloma. After 30 days of BCG (Bacillus Calmette‐Guerin) or nystatin inoculation in the left hind foot of C57B1/6 mice, there is an oscillation with a period of approximately 24 hr in the variation of paw thickness, indicating a circadian rhythm. The acrophase occurred during the light phase, between 9:00 and 13:00 hr, while the nadir occurred in the dark phase, between 21:00 and 01:00 hr. The vascular permeability around the granulomatous lesions was higher at 12:00 hr than at 24:00 hr. This is in agreement with the observation that the thickness of a paw with granulomatous lesion is larger during the light phase. This rhythmic variation was eliminated by either pinealectomy or superior cervical ganglionectomy, which greatly reduce melatonin levels in the blood. Nocturnal replacement of melatonin in pinealectomized mice led to the re‐establishment of the circadian rhythm. Thus, the rhythm of the granulomatous lesion is due to the rhythmic melatonin release by the pineal gland. This approach opens new questions regarding the modulation of chronic inflammation in inflammatory diseases that present rhythmic symptoms throughout the day.
The effect of pinealectomy on the crypts of defunctioned rat colon
Authors: Callaghan B.D.
Published: February 2007

Callaghan B.D. The effect of pinealectomy on the crypts of defunctioned rat colon. J. Pineal Res. 1997; 23:117–122. © Munksgaard, Copenhagen

Previously it has been found that 6 months after pinealectomy hyperplasia occurred in the crypt cells of the rat small bowel and colon. It is also known that defunctioning a loop of colon, using a colostomy, results in crypt cell hypoplasia, emphasizing the prime importance of luminal factors in the control of crypt cell proliferation. To determine if the effects of pinealectomy on the colon could be modified by the absence of colonic luminal contents, the crypt cell kinetic effects of combined pinealectomy and defunctioning of a colonic loop by colostomy for 6 months were examined by using a stathmokinetic technique. It was found that the hypoproliferative effect of defunctioning a loop of colon was largely but not completely overridden by the hyperproliferative effect of pinealectomy. However, previously it has been found that in the rat small bowel, the hypoproliferative effects of defunctioning a loop were completely overridden by the effect of pinealectomy. This and other evidence suggests that the role of the pineal in the control of crypt cell proliferation in the colon may possibly be different from its role in the small bowel. There is other evidence of possible involvement of the pineal in carcinoma of the colon and it is possible that its role in the colon may be to prevent excessive mitotic activity, which is known to be present in the early stages of carcinoma. The Pineal gland may have a role in modulating the usual mechanisms of crypt cell mitotic control.
Supplemental melatonin increases clonal lifespan in the protozoan Paramecium tetraurelia
Authors: Thomas John N. , Smith‐Sonneborn Joan
Published: February 2007

Thomas JN, Smith‐Sonneborn J. Supplemental melatonin increases clonal lifespan in the protozoan Paramecium tetraurelia. J. Pineal Res. 1997; 23:123–130. © Munksgaard, Copenhagen

The hypothesis that melatonin supplementation can increase the lifespan of a single‐celled organism was tested by the administration of melatonin to the ciliated protozoan Paramecium tetraurelia. Melatonin supplementation in dim red light at a dose of 0.043 mM (10 mg/L) of nutrient media (bacterized Cerophyl) per day, followed by incubation for 23 hr in darkness, increased the mean clonal lifespan of Paramecium tetraurelia in days by percentages ranging from 20.8% (P < 0.01, two‐tailed t‐test) to 24.2% (P < 0.01, ANOVA) over controls. Maximum clonal lifespan in days was also increased in melatonin‐supplemented cells, from 14.8% to 24.0% over controls. Mean clonal lifespan in fissions was not significantly greater in melatonin‐supplemented cells, with values ranging from 6.0% to 15.5% over controls. Maximum clonal lifespan in fissions did not differ appreciably, with values ranging from 1.0% to 9.1 % over controls, except in the case of cells selected for rapid division rates, in which melatonin‐supplemented cells (393 fissions) lived 20.9% longer than controls (325 fissions) in terms of cumulative cell doublings during the clonal lifespan. The finding that melatonin supplementation increased clonal lifespan in Paramecium tetraurelia, an aerobic, single‐celled organism, suggests that the mechanism of melatonin's longevity‐promoting effects may be intracellular.
Involvement of protein kinase A in the subjective nocturnal rise of melatonin release by chick pineal cells in constant darkness
Authors: Nakahara Keiko , Murakami Noboru , Nasu Tetsuo , Kuroda Haruto , Murakami Takayuki
Published: February 2007

Nakahara K, Murakami N, Nasu T, Kuroda H, Murakami T. Involvement of protein kinase A in the subjective nocturnal rise of melatonin release by chick pineal cells in constant darkness. J. Pineal Res. 1997; 23:221–229. © Munksgaard, Copenhagen

Melatonin release by chick cultured pineal cells increases during the dark periods and decreases during the light periods under light‐dark cycles, and this rhythmic secretion is maintained under constant conditions with a period of almost 24 hr. The mechanisms by which the circadian oscillator drives the melatonin rhythm under constant conditions have not been elucidated enough. We examined the possibility that cyclic AMP‐dependent protein kinase A is involved in the subjective nocturnal increase in melatonin release by chick pineal cells cultured under constant darkness. The subjective nocturnal increase of melatonin release was suppressed dose dependently by H8 (protein kinase inhibitor) and H89 (specific protein kinase A inhibitor), but not by calphostin C (specific protein kinase C inhibitor) in static cell cultures. In a cell perfusion experiment, 9 hr pulses of H8 and H89 starting at ZT 9 (CT 11.2) hr suppressed the subjective nocturnal increase in melatonin rhythm in dose‐dependent manner without causing a phase shift. An intracellular Ca2+ chelator, O,O'‐bis(2‐aminophenoxy)ethyleneglycol‐N,N,N',N'‐tetraacetic acid tetraacetoxymethyl ester (BAPTA‐AM), and extracellular Ca2+ chelators, O,O'‐bis(2‐aminophenoxy)ethyleneglycol‐N,N,N',N'‐tetraacetic acid tetrapotassium salt hydrate (BAPTA) and ethyleneglycol‐bis(β‐aminoethyl ether)‐N,N,N',N'‐tetraacetic acid (EGTA), suppressed both the subjective nocturnal increases in melatonin release and cAMP levels dose dependently. This direct evidence strongly supports the hypothesis that cAMP‐dependent protein kinase A may be involved in the subjective nocturnal increase in melatonin release by chick pineal cells and that intracellular Ca2+ plays an important role in pineal adenylate cyclase activation.
Melatonin controls superoxide anion level: Modulation of superoxide dismutase activity in ring dove heterophils
Authors: Rodríguez A. B. , Nogales G. , Ortega E. , Barriga C.
Published: February 2007

Rodríguez AB, Nogales G, Ortega E, Barriga C. Melatonin controls superoxide anion level: Modulation of superoxide dismutase activity in ring dove heterophils. J. Pineal Res. 1998; 24:9–14. © Munksgaard, Copenhagen

The pineal gland and the immune system in mammals and birds are functionally connected, with some recent findings showing that melatonin, the major secretory product of the pineal gland in vertebrates, is a free‐radical scavenger and general antioxidant. In birds, heterophils, with their ability to ingest and kill different antigens, play a central role in the host defense mechanism. This in vitro study investigated the possible antioxidant action of melatonin in heterophils isolated from adult male and female ring dove)Streptopelia risoria). The superoxide anion levels (O2−) and the superoxide dismutase (SOD) activity were evaluated as indicators of the metabolic burst of heterophils after ingestion of inert particles (latex beads) at the basal time (0 min) and 15, 30,45, and 60 min of incubation with 100 μM melatonin. The heterophil O2−levels, measured by the nitroblue tetrazolium reduction test, were lower after incubation in the presence of melatonin at all the times studied, a time‐dependent effect. Latex beads produced a significant increase in SOD activity, whereas there was a significant decrease in the presence of melatonin. In addition, when heterophils were incubated in the presence of both latex beads and melatonin, the indole appeared to annul the enhancement of SOD activity (U‐525nm) produced by latex beads. In conclusion, our findings show that the neurohormone melatonin could be a useful antioxidant.
Melatonin accelerates metamorphosis in Xenopus laevis
Authors: Rose Matthew F. , Rose Susan R.
Published: February 2007

Rose MF, Rose S.R. Melatonin accelerates metamorphosis in Xenopus laevis. J. Pineal Res. 1998; 24:90–95. © Munksgaard, Copenhagen

Delayed metamorphosis associated with large body size has been observed in Woodhousei fowleri tadpoles reared in continuous dark (DD). To evaluate the mechanism by which DD delayed metamorphosis, light‐cycle exposure was controlled and thyroxine (T4), melatonin, or drugs that alter prolactin (Prl) concentrations were given to Xenopus laevis tadpoles. It was hypothesized that exogenous melatonin would delay metamorphosis and increase body size, and that elevation of Prl concentrations would have effects similar to melatonin exposure. Xenopus laevis tadpoles were randomized to three light conditions [light/dark (LD, 12 h/12 h), DD, and continuous light (LL)] and subgroups in each light condition were treated with T4, melatonin, bromocriptine (Bro), haloperidol (Hal), or no drug. Each subgroup included 12 tadpoles. Drugs were administered in the water either continuously or daily from 07.00 to 19.00 h (Intermittent). Measurements of total length, leg length, and stage of metamorphosis were obtained at regular intervals. DD resulted in delayed metamorphosis, while LL did not. T4 accelerated metamorphosis as expected, countering the delaying effects of DD. In contrast to the hypothesis, melatonin accelerated metamorphosis and impaired body size compared to controls. Intermittent Hal also accelerated metamorphosis, while Bro delayed it. In DD, both T4 and melatonin led to increased tadpole size in contrast to their counterparts in LD or LL. Delayed metamorphosis in DD is not caused by increased melatonin production. Melatonin and Hal (as given in this study) accelerate metamorphosis. Melatonin acceleration of metamorphosis may occur through alteration of the concentration of prolactin.