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PubMed1998

The Cartesian clock metaphor for pineal gland operation pervades the origin of modern chronobiology.

In theoretical descriptions formulated during the 1600s, R. Descartes attributed a clock-like role to the pineal gland. He established the belief that pineal function underlies the laws of the universe that determine the cyclic sleep-awake states in man. Recent reports about pineal circadian pacemakers now validate the brilliant accuracy of Cartesian thought, in relation to the relevant role of the pineal gland.

Animals↗

PubMed1980

Demonstration of an endogenous circadian rhythm of alpha-melanocyte stimulating hormone in the rat pineal gland.

alpha-Melanocyte stimulating hormone (alpha-MSH) has been identified and characterized in the rat pineal gland by a combination of immunochemical and high pressure liquid chromatographic techniques. The immunoreactivity in pineal extracts was separated into two chromatographic components. The major component had a retention time identical to that of alpha-MSH while the minor component eluted just slightly before standard alpha-MSH. Male rats maintained in a 12 h photoperiod demonstrated a marked circadian rhythm in pineal alpha-MSH concentration. Concentrations that peaked at 07.00 h, 1 h after the lights were turned on, were greater than 5 times the nadir which occurred at 01.000 h. Animals house in chronic dark for 7 days maintained the diurnal variation of alpha-MSH concentrations. However, in chronically dark housed rats, the peak shifted to 05.000 h and was greater than 10 times the nidir of this rhythm and approximately 4 time the peak at 07.00 in alternating light/dark conditions. Rats exposed to chronic light for 7 days maintained a pineal alpha-MSH rhythm although the amplitude of the peak was significantly decreased compared to the rhythm in animals housed in alternating light/dark conditions. Neither hypophysectomy nor superior cervical ganglionectomy had any effect on the alpha-MSH rhythm. Lesion of the arcuate nucleus, the major source of alpha-MSH-containing nerves in the brain, did not significantly affect pineal alpha-MSH concentrations. These data demonstrate a circadian alpha-MSH rhythm in the rat pineal and suggest an alpha-MSH involvement in the rhythmic processes of the pineal gland.

Animals↗

PubMed1995

The mammalian pineal gland and reproduction. Controversies and strategies for future research.

Evidence for a role of the pineal gland and its major hormonal product, melatonin, in mammalian reproduction has accumulated for over three decades. In sorting through the masses of data pertaining to this issue, certain facts are becoming established. For example, the pineal gland is clearly involved in seasonal reproductive cycles via transduction of daylength (more properly nightlength) information in the form of plasma melatonin rhythms. Specific melatonin receptors are found in the hypothalamus and pituitary pars tuberalis of most of the mammalian species examined thus far. Melatonin's mode of action on the reproductive axis is quite variable but may, in many cases, involve modulation of gonadotropin-releasing hormone secretion from the median eminence. Clinical evidence continues to support the idea that melatonin may play a role in the timing of puberty.

Animals↗

PubMedDate not supplied

Failure to stimulate melatonin synthesis in the rat pineal gland with an adenosine analog.

Recent studies indicate the presence of adenosine binding sites in rat pinealocytes and an effect of their activation on pineal serotonin metabolism. However, controversial data exist, and reports suggest that the role of adenosine in pineal physiology is complex. On this basis, we evaluated the effects of an adenosine analog (N-ethyl-carboxamido-adenosine: NECA) on in vitro and in vivo melatonin production in the rat pineal gland. In the in vitro protocol, pineals were incubated with NECA (0.5 mM, 1 mM, or 2.5 mM) or isoproterenol (ISO: 10(-6)M) for 4 hr. In the in vivo experiments, animals were given NECA (1 mg/kg IP), ISO (0.5 mg/kg IP) or 1 ml saline diluent and sacrificed 2 hr later. The samples were assayed for pineal N-acetyltransferase (NAT) activity and melatonin concentrations. ISO caused the expected marked rise in NAT activity and melatonin levels in both protocols. NECA was ineffective in causing any modification of the parameters measured. We conclude that the adenosine analog NECA may not be involved in the activation of melatonin production. These data contrast with others in which NECA administration resulted in an increase in melatonin levels. The participation, if any, of the purinergic system in the physiology of the pineal gland is still far from being characterized.

Adenosine↗

PubMedDate not supplied

Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland.

Arginine vasopressin (AVP) and oxytocin (OT) as well as their CNS carrier neurophysins (Np) have been found in the pineal gland. In view of the analogy between the pineal gland and the retina, the contents of these neuropeptides in rat, human and bovine retinae were determined. AVP, OT and Np were detected by specific radioimmunoassay (RIA) and their presence confirmed by RIA measurements (1) in rat and human retinae on HPLC fractions and (2) by the detection of the C-terminal portion of the precursor to AVP and its associated Np = propressophysin (CPP). The AVP and OT content in the retina of the rat was modified by light: AVP and OT content was smaller at 2 a.m. than at 2 p.m., but was increased by a 7 day constant exposure to darkness. In contrast, pituitary content was decreased after 7 days of constant darkness. If one optic nerve was cut we observed a decrease in retinal AVP content compared to the contralateral side and a decrease in pituitary AVP content. Our data clearly demonstrated the presence of AVP, OT and Np in the retina and their variation induced by light. It is probable that these peptides are of central origin.

Animals↗

PubMed1994

Clonidine in vivo mimics the acute suppressive but not the phase-shifting effects of light on circadian rhythm of serotonin N-acetyltransferase activity in chick pineal gland.

Comparative in vivo studies on effects of pulses of light and clonidine, a selective agonist of alpha 2-adrenergic receptors, on the circadian rhythm of serotonin N-acetyltransferase (NAT) activity in chick pineal gland were performed. Six-hour pulses of white light caused an acute suppression of the nocturnal NAT activity and phase-dependent phase shifts of the circadian rhythm of the enzyme activity relative to controls. Systemic administration of clonidine acutely suppressed NAT activity of chick pineal gland, but did not affect the phase of subsequent cycles in constant darkness. These results give further support to the concept based on in vitro studies that alpha 2-adrenergic receptors are involved in regulation of melatonin biosynthesis in chick pineal gland by a mechanism distal to the pacemaker that generates the circadian melatonin rhythm.

Animals↗

PubMed1997

Innervation of the sheep pineal gland by nonsympathetic nerve fibers containing NADPH-diaphorase activity.

We used the NADPH-diaphorase histochemical method as a potential marker for nitric oxide synthase (NOS)-containing nerve fibers innervating the pineal gland of the sheep. Nerve fibers containing NADPH-diaphorase activity provide dense innervation of the sheep pineal gland. The nerve fibers were located in the pineal capsule, in the connective tissue septae separating the lobull of the gland, and penetrating between the pinealocytes. The nerve fibers were either smooth or endowed with boutons en passant. After bilateral removal of the superior cervical ganglion, the dense network of NADPH-diaphorase-positive fibers was still present in the gland. Ganglionectomy affected neither the distribution nor the appearance of the NADPH-diaphorase-positive fibers. Most of the NADPH-diaphorase-positive fibers also contained peptide histidine isoleucine and vasoactive intestinal polypeptide, and a comparatively smaller fraction contained neuropeptide Y. Pinealocytes never exhibited NADPH-diaphorase activity. These results demonstrate a major neural input to the sheep pineal gland with NADPH-diaphorase-positive nerve fibers of nonsympathetic origin.

Animals↗

PubMed1992

Coexpression of vimentin and glial fibrillary acidic protein in glial cells of the adult rat pineal gland.

In the present work, coexpression of vimentin (VIM) and glial fibrillary acidic protein (GFAP) is demonstrated in the glial cells of the adult rat pineal gland. Serial consecutive Epon semithin sections (0.5 microns thick) were alternately immunostained for VIM and GFAP. GFAP positive cells and processes were found in the proximal region of the pineal gland, near the pineal stalk. Most of these cells were also immunostained for VIM in adjacent semithin sections. The significance of the coexpression VIM-GFAP and the restricted location of GFAP positive cells is discussed in relation with the maturation of pineal glial cells.

Animals↗

PubMed1981

Circadian variation of cyclic AMP in the rat pineal gland.

This study was carried out to investigate circadian variation of cyclic AMP contents in the rat pineal glands, using the high-energy microwave radiation technique. The pattern of cyclic AMP concentration in the pineal gland showed a distinct circadian variation, with the maximum level at 0200 and the lowest at 1400. The administration of propranolol completely blocked the dark-induced increase in the pineal cyclic AMP level at 0200, and the administration of isoproterenol induced a threefold, rapid increase in the cyclic AMP level at 1400, although it did not change the level at 0200.

Animals↗

PubMedDate not supplied

Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina.

The mRNAs encoding three enzymes of the melatonin synthesis pathway (tryptophan hydroxylase (TPH), arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyl-transferase (HIOMT)) are expressed with a day/night rhythm in the chicken pineal gland and retina. TPH and AANAT mRNA levels reach their peak at night. HIOMT mRNA levels peak at night in the retina, but during the day in the pineal gland. In this tissue, the rhythm of TPH, AANAT and HIOMT mRNA levels persisted in constant darkness (DD), both in vivo and in vitro, indicating that the three genes are controlled by the circadian oscillator of the chicken pineal. In the retina, the rhythms of TPH and AANAT mRNA levels also persisted in DD in vivo, suggesting that they are driven by a circadian oscillator. In contrast, the rhythm of HIOMT mRNA in the retina appeared to be controlled only by light. The clones of chicken AANAT and HIOMT genes that we have isolated should help us to understand the molecular mechanisms of: 1) their transcriptional regulation by circadian oscillators and by light; 2) their tissue-specific expression in the pineal gland and the retina.

ARNTL Transcription Factors↗

PubMed1986

Inverse behaviour of "synaptic" ribbon and spherule numbers in the pineal gland of male guinea-pigs exposed to continuous illumination.

There is increasing evidence that pineal "synaptic" ribbons are a heterogeneous population of organelles. In addition to "synaptic" ribbons (SR) sensu stricto, which consist of an electron-dense rod surrounded by electron-lucent vesicles, "synaptic" spherules (SS) exist, the electron-dense core of which is round and much wider than that of the SR. In the guinea-pig SR and SS numbers exhibit an inverse day/night rhythmicity. To gain more insight into the functional significance of SR and SS, guinea-pigs were exposed to continuous illumination for approximately 4 months (LL) and the respective structures in the pineal gland were quantitated under the electron microscope and compared with control animals kept under a lighting regimen of 12 h light and 12 h dark. It was found that SR numbers increase following LL whereas SS numbers decrease. The proximal, intermediate and distal parts of the dumbbell-shaped organ respond differently. The increase in SR numbers is significant in the distal and intermediate regions only, whereas the decrease in SS numbers is significant in the proximal and the intermediate regions only. Within each pineal region analyses of parenchymal subareas measuring 65 microns by 65 microns exhibit an inverse correlation of SR and SS numbers indicating that there are parenchymal domains in which either SR or SS predominate. Morphometric analyses of a number of pinealocytic parameters reveal minor differences between different pineal regions and that exposure to LL does not strikingly affect the pinealocyte perikarya. By contrast, the numbers of pinealocyte processes increase significantly after LL in the distal and intermediate, but not the proximal region of the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Postnatal changes in adrenergic and neuropeptide Y-containing nerve fibres in pineal gland of the pig. An immunohistochemical study.

Postnatal development of the innervation of the porcine pineal gland by tyrosine hydroxylase-(TH-), dopamine-beta-hydroxylase-(D beta H), phenylethanolamine-N-methyltransferase-(PNMT-) and neuropeptide Y- (NPY-) immunoreactive (IR) nerve fibres was examined using the double-labelling immunohistochemical technique. TH-IR nerve fibres appeared in the pineal gland of new-born piglets and formed plexus in the capsula and connective tissue septa of the gland. In 20-day-old pigs and older ones, the nerve terminals branched off from the plexus and penetrated into adjacent parenchyma. The nerve fibres formed network; its density increased with age and depended on the region of the gland. In mature pigs, some differences in the innervation pattern between cortex and medulla were also observed. Most of TH-IR fibres were also D beta H- and NPY-positive. Some PNMT-positive fibres were noted in new-born piglets, but not in older animals. NPY-IR fibres were distributed in pattern overlapping that observed in the case of TH- and D beta H-IR fibres. Most of NPY-IR fibres were also positive for TH.

Adrenergic Fibers↗

PubMed1993

Effects of the pineal gland on the growth processes of Guerin epithelioma in male Wistar rats.

The effects of pinealectomy (PX) and melatonin (Mel) administration on the growth processes of Guerin epithelioma, a malignant tumour derived from spontaneous cancer in Wistar rat uterus, was investigated in five groups of male rats. The mean life span of the rats bearing Guerin tumours (GT) and subjected to PX was shorter than in animals with an intact pineal gland. Mel did not affect the lifespan in rats with intact pineals or in those subjected to PX. Mel decreased the mitotic activity of GT cells in rats with and without the pineal gland. Pathomorphological examination revealed high malignancy of the primary tumour but no metastases. The results confirmed the important role of the pineal gland in 'oncostasis'.

Animals↗

PubMed1987

Pineal gland and ocular influences on turkey breeder hens. 1. Reproductive performance.

The influence of the pineal gland and the eyes on reproductive performance of turkey hens was examined. Photosensitive, yearling Large White turkey breeder hens underwent pinealectomy (PX) or bilateral ocular enucleation (EX) or both while held on 8 hr of light per day (8L:16D) and were then photoinduced into a typical 20-week egg laying period by exposing the birds to 16 hr of light per day (16L:8D). Data were obtained for the time to first egg (sexual maturation), rate of egg laying, percent fertility, percent hatchability, weight of poults at hatching, and plasma melatonin levels. A significant interaction between PX and EX treatments occurred in the sexual maturation data only. Pinealectomy significantly delayed (P less than .05) the onset of egg laying (by 4.1 to 7.4 days) compared with the other treatment groups. No other significant differences in onset of lay occurred. Pinealectomy significantly depressed egg production during weeks 11 to 20 of lay and this resulted in fewer eggs per PX hen over the 20-week study (85.4 vs. 93.3 eggs in the PX and pineal intact groups, respectively). Enucleation did not significantly affect egg production. Neither the PX nor the EX treatment significantly affected fertility or hatchability determined at 4-week intervals over the 20-week study. However, poult weights were significantly greater as a result of either PX (P less than .01) or EX (P less than .05) treatment. Nocturnal elevation of plasma melatonin was significantly reduced by PX but not by EX. It was concluded that an extraretinal, extrapineal photoreceptive mechanism is operative in turkey breeder hens but both the pineal gland and the eyes can influence certain reproductive parameters.

Animals↗

PubMed1999

Effects of static electromagnetic fields on chick embryo pineal gland development.

The effects of static electromagnetic fields on the development of the chick embryo pineal gland were studied. A total of 144 fertilized White Leghorn eggs were sacrificed after 5, 10 and 15 days of incubation. The stage of development was determined in all embryos using the Hamburger and Hamilton method [J Morphol 49: 88-92, 1951]. The various morphometric parameters (diameter and distance of the pineal gland and its lumen) were measured on serial 7-micron-thick sections. The data were obtained in a morphometer and processed statistically. The intensities of the static electromagnetic fields were 18 and 36 mT. Control and exposed embryos were equally distributed and randomly assigned. After 5 days of incubation, 25% of embryos exposed to a static electromagnetic field of 18 mT had a more advanced stage of development than controls and embryos exposed to 36 mT. On the 10th and 15th day, embryos exposed to either 18 or 36 mT tended to be more developed than controls. In the morphometric study, results were similar for the controls and exposed embryos after 5 and 10 days of incubation. However, the values of the 15-day-old embryos exposed to static magnetic fields were lower than the values of the controls (p > 0.01). These differences were more pronounced in the embryos exposed to 36 mT. These results seem to indicate that static electromagnetic fields affect the development and growth of embryos unequally, and that their action can depend not only on the intensity of the static electromagnetic field, but also on the length of exposure and the organ which is developing. It may be interesting to use these data in ultrastructural and physiological studies.

Animals↗

PubMed1971

A cyclic AMP-dependent protein kinase of the bovine pineal gland.

A protein kinase that is dependent on cAMP was found to be present in significant amounts in rat and bovine pineal glands. This enzyme system was isolated from bovine pineal glands and shown to consist of two proteins, a kinase and a cAMP-binding protein. The kinase primarily phosphorylates histones and may function in the control of the diurnal variation of the enzymes in the melatonin biosynthetic pathway.

Adenosine Triphosphate↗

PubMed1983

Photoperiodic regulation of serotonin N-acetyltransferase activity in the pineal gland of the chicken.

1. In continuous light, serotonin N-acetyltransferase activity in the pineal gland of 16-day-old chicks was reduced to about a half of the usual nocturnal level only in the first day, but no suppressive effect by the light was observed throughout the following 2 days. 2. In continuous darkness, circadian N-acetyltransferase rhythm persisted for three consecutive days. 3. In continuous light, the phase of N-acetyltransferase rhythm in chick pineal delayed remarkably for three consecutive days, while the phase delayed in a lesser degree in continuous darkness. 4. The rhythm of N-acetyltransferase activity in the pineal gland of 13-day-old chicks was entrainable to a shorter (8L: 8D) and a longer (18L: 18D) photoperiod as in a 12L: 12D photoperiod, but a shorter photoperiod such as a 3L: 3D photoperiod failed to change the pre-established 12L: 12D rhythm.

Acetyltransferases↗

PubMed1998

Characterization of the multisynaptic neuronal control of the rat pineal gland using viral transneuronal tracing.

Knowledge of the polysynaptic pathway conveying photic information to the pineal gland is based upon studies employing lesions, knife cuts and classical tracers. In the present investigation we used viral transneuronal tracing to re-examine the organization of this circuitry. This was accomplished by injecting a neurotropic alpha herpesvirus (pseudorabies virus) into the gland and localizing viral antigen in infected neurones at various postinoculation intervals. This approach is based upon the demonstrated ability of this virus to invade axon terminals, replicate in neurones and pass retrogradely through a multisynaptic circuit. Immunohistochemical localization of viral antigen revealed the progressive appearance of infected neurones in the superior cervical ganglion (SCG), intermediolateral nucleus of the upper thoracic spinal cord (IML), parvicellular subdivisions of the hypothalamic paraventricular nucleus (PVN), and the suprachiasmatic nucleus (SCN). Other infected cell groups known to project to the IML also became infected. Infection of the PVN reproducibly involved neurones in the dorsal, medial and lateral parvicellular subdivisions and preceded the appearance of infected neurones in the SCN and other regions of hypothalamus. Topographic analysis of virus infected neurones within the SCN revealed differential infection of SCN subdivisions that suggested topography in the projection of the SCN to the PVN. Removal of the SCG eliminated infection within the aforementioned circuitry and revealed a parasympathetic innervation from the sphenopalatine ganglion. The data provide further detail on the cellular identity and synaptology of neural circuitry controlling the rhythmic secretion of melatonin by the rat pineal gland.

Animals↗