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At least 235 records · Page 13Linked to original sources

PubMed2004

Opsin photoisomerases in the chick retina and pineal gland: characterization, localization, and circadian regulation.

PURPOSE: The chick retina and pineal gland exhibit circadian oscillations in biochemical and physiological processes in vivo and in vitro, which entrain to 24-hour light-dark cycles. However, the phototransduction mechanisms responsible for entrainment are largely unknown. The present study characterizes two candidate opsinlike genes that may play a role in entrainment of the clocks in these tissues. METHODS: Bioinformatics, cladistic techniques, and in situ hybridization and Northern blot analyses were conducted to characterize, localize, and determine the circadian expression of the candidate opsinlike genes in the retina and pineal gland. RESULTS: Two candidate photosensors and/or photoisomerases were predominantly distributed within the pineal gland and retina: the retinal pigmented epithelium-derived rhodopsin homologue (peropsin, gRrh) and retinal G-protein-coupled receptor opsin (RGR opsin, gRgr). Northern blot and in situ analyses revealed mRNA expression for both opsins in the pineal gland, retina, and brain tissue. The mRNA for both genes within the pineal gland and retina is regulated on a circadian basis such that they are highest in late subjective day. Digoxigenin in situ analyses showed retinal gRgr message within the inner nuclear layer (INL) and retinal ganglion cell layer (RGL), whereas gRrh message was distributed predominantly in the RGL. In the pineal gland, gRgr message was sparsely distributed among pinealocytes in follicles, but not within the follicles themselves, whereas gRrh was localized in interstitial areas indicative of astrocytic and/or endothelial origin. CONCLUSIONS: The presence of two putative photoisomerases within the pineal gland and in retinal layers associated with biological clock function provides two candidate opsinlike genes that may serve in the visual cycle regulation of the circadian clock.

Amino Acid Sequence↗

PubMed1986

Studies on high-affinity [3H]substance P binding sites in bovine pineal gland.

The presence of substance P in numerous mammalian pineal glands prompted us to search for its binding sites in the bovine pineal gland. The binding assays to pineal membrane were carried out in polypropylene microcentrifuge tubes in a final volume of 500 microliters of 50 mM Tris-HCl buffer (pH 7.4) containing aliquots of 200-500 micrograms protein, 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, and 50 microliters of [3H]substance P (3H-SP, 45.7 Ci/mmol to yield a final concentration of 0.02-20 nM) to start the reactions, which were incubated for 20 min at 20 degrees C. The reactions were terminated by centrifugation in a Fisher Microcentrifuge Model 235A for 30 seconds at 13,000 X g, and the pellets were washed twice with 1 ml of ice-cold 50 mM Tris-HCl buffer containing 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, and 1 mM CaCl2. The bottoms of the tubes were cut, the membrane pellets were dissolved in 5 ml of Triton X-100/toluene fluor (1:3) scintillation fluid, and the radioactivity was counted. The specific [3H]-substance P binding at 1-2 nM was 40-50% of the total binding, and the non-specific binding was assessed by using 2 microM of unlabelled substance P. These studies identified in bovine pineal gland a high affinity receptor site for [3H]SP with a KD value of 0.43 nM and a Bmax value of 71.14 fmol/mg protein. The relative affinity of various substance P analogues or fragments was: substance P greater than physalaemin greater than SP2-11 greater than SP3-11 greater than SP4-11 greater than SP6-11 greater than substance K = eledoisin greater than kassinin greater than SP7-11 greater than SP free acid. Substance P did not alter the basal or the norepinephrine-induced stimulation of the activity of serotonin N-acetyltransferase in rat pineal gland in culture.

Animals↗

PubMed1997

Immunohistochemical and tracer studies of macrophages/microglia in the pineal gland of postnatal rats.

The pineal gland of rats of various ages (1-21 days old) was examined by immunohistochemistry and electron microscopy. Numerous widely distributed cells identified as macrophages/microglia were immunoreactive with the monoclonal antibodies OX-42, OX-18, OX-6, and ED1, indicating that they expressed complement type 3 (CR3) receptors, major histocompatibility complex class I and II antigens, and antigens of monocyte/macrophage lineage as detected by the antibodies, respectively. Following an intraperitoneal injection of rhodamine isothiocyanate (RhIC) in all age groups, the cells emitted a bright fluorescence. They were also labeled by horseradish peroxidase (HRP), as demonstrated in both light and electron microscopy. An HRP reaction was observed in vesicles and lysosomes at the ultrastructural level. A remarkable feature was the uptake of these tracers by pinealocytes. In light microscopy, the pinealocytes showed a punctate reaction product 3-24 hours after HRP injection. By electron microscopy, the reaction product was observed in vesicles, lysosomes, and some rod-like structures in the cytoplasm. On the basis of their immunophenotypic features, it is suggested that the macrophages/microglia in the pineal gland are active phagocytes which are also probably involved in the immunoregulatory function in the gland. The avid uptake of RhIC and HRP from the circulation by these cells suggests that serum-derived substances that may gain access to the parenchyma of the gland are being constantly monitored. The labeling of pinealocytes with HRP suggests that the functional activities of these cells are being modulated by serum-derived substances.

Animals↗

PubMed1976

The degree of calcification and the weight of pineal glands in Ugandan Africans.

Two hundred formalin fixed, isolated pineal glands from Ugandan Africans have been X-rayed in consecutive unselected post mortems using a laboratory X-ray machine. The degree of calcification has been divided into four stages and according to this up to 43% of all pineal glands after the age of 10 years are likely to be detected in an ordinary skull X-ray. In females the pineal glands have been more often calcified and heavier than in males, however the stalk of pineal glands in males has shown more frequent calcifications than in females. The average weight per decade has been almost constant throughout the life span. In Ugandan Africans the pineal glands were significantly lighter than in Caucasians and possible reasons for this feature are discussed.

Black People↗

PubMed1995

Volume of the pineal gland in schizophrenia; an MRI study.

Pineal gland abnormality has been proposed as a possible biological defect in schizophrenia. This study was designed to investigate volumetric differences of the pineal gland using Magnetic Resonance Imaging (MRI). Patients with a DSM-III-R diagnosis of schizophrenia or schizophreniform disorder (n = 45) and normal controls (n = 86) were scanned using a 1.5 Tesla scanner. The volume of the pineal was obtained by blind manual tracing of the gland on T1 weighted images, using locally developed software, BRAINS. The inter-rater reliability (n = 25) yielded an intraclass r of 0.92. Comparison of the volumes by t-test showed no significant difference between patients and normal controls (p = 0.77). This study, backed by a large sample size, suggests that there are no volumetric differences between schizophrenic patients and controls in regard to the pineal gland.

Adult↗

PubMed1984

Effects of methotrexate on biopterin levels and synthesis in rat cultured pineal glands.

Culture of rat pineal glands in methotrexate (0.5, 5, or 10 microM) for 6 or 24 h did not alter pineal tetrahydrobiopterin (85-90% of total biopterin in cultured glands), except for a decrease of 30% after 24 h culture in 10 microM methotrexate. However, pineal dihydrobiopterin and/or biopterin (10-15% of total biopterin) was increased by methotrexate up to 2.5-fold. Biopterin detected in the culture medium following pineal culture was also increased to a similar extent after methotrexate treatment and appeared to represent leakage of pineal dihydrobiopterin and/or biopterin. Culture of glands in 5 microM methotrexate did not alter the conversion of [U-14C]-guanosine to [14C]biopterin, suggesting that pineal tetrahydrobiopterin synthesis was not altered by methotrexate. Complete inhibition of dihydrofolate reductase activity measured in pineal homogenates was obtained following culture of glands in all concentrations of methotrexate studied. Therefore, dihydrofolate reductase and dihydrobiopterin do not appear to be involved in a major biosynthetic pathway for pineal tetrahydrobiopterin from GTP, although they may have a minor role in tetrahydrobiopterin synthesis.

Animals↗

PubMed2002

[Aging of the pineal gland].

The age-related changes in the pineal gland are functional rather than organic, which makes their correction or prevention more tenable. The amelioration or inhibition of some age-related impairments of the pineal gland were observed with dietary restriction and the use of S-adenosylmethionine or MAO-A inhibitors. A threefold increase in nocturnal melatonin peaks occurs in old rhesus monkeys treated with a synthetic peptide Ala-Glu-Asp-Gly (Epithalon) designed basing on the amino acid content of a pineal peptide extract Epithalamin. Other effects of Epithalon markedly overlap with melatonin effects. Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland.

Aging↗

PubMed2006

Molecular cloning, mRNA expression, and immunocytochemical localization of a putative blue-light photoreceptor CRY4 in the chicken pineal gland.

In non-mammalian vertebrates, the pineal gland contains an endogenous circadian oscillator and serves as a photosensitive neuroendocrinal organ. To better understand the pineal phototransduction mechanism, we focused on the chicken putative blue-light photoreceptive molecule, Cryptochrome4 (cCRY4). Here we report the molecular cloning of pineal cCry4 cDNA, the in vivo expression of cCry4 mRNA, and the detection of cCRY4 protein. cCry4 is transcribed in a wide variety of chick tissues out of which the pineal gland and retina contain high levels of cCry4 mRNA. In the pineal gland, under 12 h light : 12 h dark cycles, the levels of both cCry4 mRNA and cCRY4 protein showed diurnal changes, and in cultured chick pineal cells, the cCry4 mRNA level was not only up-regulated by light but also controlled by circadian signals. Immunoblot analysis with a cCRY4-specific antibody detected cCRY4 in a soluble fraction of the pineal lysate. Immunocytochemistry revealed that cCRY4 was expressed in many parenchymal cells and a limited number of stromal cells. These cCRY4 features strikingly contrast with those of the chick pineal photoreceptor pinopsin, suggesting a possible temporal and/or spatial duplicity of the pineal photoreceptive system, the opsin- and CRY-based mechanisms.

Animals↗

PubMed2003

[Current view of the pineal gland].

Knowledge of the pineal, like that of other biological structures, has progressed from speculative to concrete information. A number of general roles have been suggested for the pineal gland over the years based on anatomical observations, studies of function and studies of biochemistry. We study the knowledges about the pineal before and after the successfully discovery of the melatonin by Lerner in 1958. Melatonin has recently been shown to have high antioxidative propies. Adriamycin, an antracyclinic antibiotic frequently used in quimiotepeutic treatments is highly toxic; it inhibits protein synthesis and provokes prooxidant effects. We tested the protective effects of melatonin against adriamycin toxicity in the rat. Our results demonstrate that oxidative damage induced by the antitumor drug, adriamycin, can be reduced by low pharmacological doses of melatonin.

Animals↗

PubMed2003

Transcriptional profiling of the chick pineal gland, a photoreceptive circadian oscillator and pacemaker.

The avian pineal gland contains both circadian oscillators and photoreceptors to produce rhythms in biosynthesis of the hormone melatonin in vivo and in vitro. The molecular mechanisms for melatonin biosynthesis are largely understood, but the mechanisms driving the rhythm itself or the photoreceptive processes that entrain the rhythm are unknown. We have produced cDNA microarrays of pineal gland transcripts under light-dark and constant darkness conditions. Rhythmic transcripts were classified according to function, representing diverse functional groups, including phototransduction pathways, transcription/translation factors, ion channel proteins, cell signaling molecules, and immune function genes. These were also organized relative to time of day mRNA abundance in light-dark and constant darkness. The transcriptional profile of the chick pineal gland reveals a more complex form of gene regulation than one might expect from a gland whose sole apparent function is the rhythmic biosynthesis of melatonin. The mRNAs encoding melatonin biosynthesis are rhythmic as are many orthologs of mammalian "clock genes." However, the oscillation of phototransductive, immune, stress response, hormone binding, and other important processes in the transcriptome of the pineal gland, raises new questions regarding the role of the pineal gland in circadian rhythm generation, organization, and avian physiology.

Animals↗

PubMed1984

Does maximal serotonin N-acetyltransferase activity necessarily reflect maximal melatonin production in the rat pineal gland?

p-Chlorophenylalanine (PCPA) treatment reduced pineal 5-hydroxytryptamine (5-HT) levels by 68.9% of non-PCPA treated levels in intact rat pineal glands and by 95.9% of non-PCPA treated levels in adrenergically denervated rat pineal glands. Although isoproterenol stimulation resulted in increased activity of serotonin N-acetyltransferase (NAT) activity in all experimental groups, pineal melatonin production was maximal only in non-PCPA treated rats, suggesting that 5-HT concentrations may exert considerable influence on the level of melatonin production in the rat pineal gland, independent of the level of NAT activity.

Acetyltransferases↗

PubMed1992

Sympathetic denervation and chronic serotonin uptake blockade by fluoxetine do not affect pineal gland 5-hydroxyindole acetic acid: evidence that oxidative deamination of pineal serotonin is a property of the pinealocyte.

This investigation tested the hypothesis that oxidative deamination of 5HT in the pineal gland occurs primarily in cellular compartments other than the pinealocyte (i.e., noradrenergic nerve terminals and glia). Following sympathetic denervation of the pineal gland by bilateral superior cervical sympathectomy, pineal levels of 5HT and its oxidative metabolite, 5HIAA, were measured by HPLC from samples collected at six time points over the 24 h photoperiod. The role of glia in 5HT deamination was further examined by chronic treatment with the 5HT uptake blocker, fluoxetine (10 mg/kg). Sympathectomy abolished the circadian rhythms of both 5HT and 5HIAA, but had no statistically significant effect on the ratio of 5HIAA/5HT compared to sham-operated and intact controls over the 24 h period. Pineal daytime levels of both 5HT and 5HIAA were unaffected by fluoxetine treatment. These findings indicate that the pinealocyte is an important cellular compartment for 5HT oxidative metabolism.

Animals↗

PubMed1995

Evidence for a regulatory role of melatonin on serotonin release and uptake in the pineal gland.

Melatonin has been proposed to exert some regulatory actions within the pineal gland itself. The present study examined the effect of melatonin on the release of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) from rat pineal glands by using an in vitro perifusion system. Melatonin induced a concentration-dependent stimulatory effect on 5-HT secretion from 10(-6) M to 10(-3) M. Maximal effects were obtained with melatonin 10(-3) M and concentrations lower than 10(-6) M were without effect. The secretion of 5-HIAA was inhibited by melatonin 10(-3) and 10(-4) M, but it was increased when pineals were incubated with 10(-5) and 10(-6) M of melatonin. The indoleamine secretion was also studied on peripherally denervated rat pineal glands. Basal output of 5-HT from these glands was increased when compared with those from control rats. In contrast, the secretion of 5-HIAA was strongly reduced after removal of the sympathetic input to the pineal gland. Melatonin 10(-3) M failed to stimulate 5-HT release from denervated pineal glands, although it inhibited 5-HIAA secretion. In contrast, melatonin 10(-5) M enhanced 5-HT release without altering 5-HIAA output. Fluoxetine, a 5-HT uptake inhibitor, produced similar effects than mM concentrations of melatonin on the indoleamine secretion from control pineal glands, but it had no effect on glands taken from peripherally denervated rats. These data suggest that mM concentrations of the pineal hormone are able to stimulate 5-HT release from the pinealocyte, while mM concentrations of melatonin increase extracellular 5-HT by inhibiting its reuptake in the adrenergic nerve endings. These findings are discussed in relation to the possible role of melatonin regulating the intra- and extracellular availability of 5-HT in the pineal gland and its significance as an autocrine factor.

Animals↗

PubMed1980

Circadian rhythms of melatonin release from individual superfused chicken pineal glands in vitro.

The pineal gland of birds contains one or more circadian oscillators that play a major role in overall temporal organization. We have developed a flow-through culture system for the isolated pineal by which we can measure the release of melatonin continuously from superfused glands over long periods of time. Chicken pineals release melatonin rhythmically, and these rhythms persist in vitro with a circadian oscillation. In light cycles the release of melatonin is strongly rhythmic; however, in constant conditions the amplitude of the rhythm is lower and appears to be damping. Light has at least two effects upon the isolated pineal: cyclic light input synchronizes the rhythm, and acute light exposure at night rapidly inhibits melatonin release. The cultured avian pineal clearly offers great potential as a model system for the study of vertebrate circadian oscillators and may open the way for an analysis of mechanism.

Animals↗

PubMed1998

Daily and seasonal variations in the concentration of melatonin in the human pineal gland.

To elucidate whether pineal melatonin secretion is affected by changes in day length, we determined the concentration of melatonin in human pineal glands obtained at autopsy from 66 male subjects, aged 16-84 years over a period of 12 consecutive months. Based on the time of death, a day-night difference in pineal melatonin levels was evident only in the long photoperiod (April-September) with significantly higher melatonin concentrations occurring at night (2200-1000 h). Nighttime values in the long photoperiod were significantly higher than the nighttime values during the short photoperiod (October-March). During the short photoperiod, the data suggested a possible phase-delay in melatonin secretion. Day-night difference was evident in young subjects (30-60 years), but not in elderly subjects (61-84 years). Elderly subjects had lower total melatonin levels (day and night values) although statistically not significant. Therefore, melatonin levels did not decline with age and when the data were analyzed by age there was no significant day-night difference in melatonin levels. These data indicate that the concentration of melatonin in the human pineal is augmented only during the long photoperiod. The results suggest a partial effect of photoperiod on melatonin secretion in humans. This may result from living in an artificial light environment or due to other nonphotic signals involved in generating melatonin rhythm.

Adolescent↗

PubMed2000

Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin in the chick pineal gland.

In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting in constant darkness and have opposite phases. Acute exposure of chicks to white light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal 5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light (100 lux) applied early in the subjective night (CT12-CT18) caused a delay in the phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and 4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse was given during the late subjective night (C18 CT24) it advanced the phase of the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In the chick pineal the phase-advancing effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin were more pronounced than the phase-delaying effects. Our results provide the first evidence that light is capable of phase shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the melatonin rhythm.

Animals↗

PubMed1981

Morphological and electrophysiological evidence for habenular influence on the guinea-pig pineal gland.

The central innervation of the guinea-pig pineal gland was investigated by histological and electrophysiological methods: Staining the pineal gland and the epithalamus, a double route of central innervation could be shown in the anterior part of the organ: (a) Fibres from the habenular nuclei, mainly from the lateral part, penetrate the organ via the pineal stalk. (b) Other fibres join the striae medullares and running in the habenulae reach the organ more dorsally. The fibres end in the intercellular space where they form a dense network. In 15 male guinea-pigs under urethane anesthesia, two series of unit recording experiments were performed: (a) Recordings were made from 128 units in the posterior and anterior part of the pineal gland and the effects of electrical stimulation of the habenular nuclei were observed. Lateral habenular stimulation influenced 44% of the units. 80% of these were excited and 20% were inhibited. (b) Recordings were made from 42 units in the lateral habenular nucleus. Twelve units (29%) responded with an augmentation of spontaneous activity following pineal gland stimulation. No inhibition response was observed.

Animals↗

PubMed1990

Oncostatic effects of the pineal gland.

There is increasing evidence that the pineal gland has a role in the control of neoplastic processes. Kerenyi found hyperplasia of the pineal gland in patients with widely disseminated malignant melanoma. Feuer and Kerenyi reported significantly higher serum melatonin levels with malignant melanoma. Beral et al. found 2.1 times increased risks of melanoma and Pasternak et al. described a relative risk of 1.87, related to exposure to fluorescent light. In our study, white New Zealand rabbits were exposed for 12 months to fluorescent light. The serum melatonin levels of the control group were significantly higher, p less than 0.005. According to Cohen, the pineal gland has a role in the etiology of breast cancer. Melatonin inhibits MCF-7 human breast cancer cell growth in culture. In our study of 500 surgically removed breast tumors, 254 were melatonin receptor positive, 246 negative. Most melatonin receptor positive breast cancer occurred between 60-65 years of age, receptor negative breast cancer peaked between 40-45 years. Benign breast tumors were almost invariably melatonin receptor positive. It is proposed that melatonin may have a direct effect on breast tumors, the melatonin receptors being the probable sites of interaction between melatonin and the tumor cell.

Animals↗