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Melatonin: parallels in pineal gland and retina.

It is apparent that several relationships exist between the pineal gland and retina. The similarities in development and morphology have been obvious for many years. A recent resurgence of interest in this field has led to a further understanding of many functional similarities between these two organs. A notable feature of the pineal gland and retina is their common ability to synthesize the indolamine hormone, melatonin. Many investigators suspect that the cyclic rhythm of retinal melatonin synthesis may be related to other cyclic events which normally occur in the retina.

Acetylserotonin O-Methyltransferase↗

Large cysts of the pineal gland: report of two cases.

Two cases of large, nontumorous cysts of the pineal gland are reported, the histopathology of which was confirmed using surgically resected specimens. Both patients were middle-aged, and the pineal cysts were found incidentally. The histopathological findings in the two cases were strikingly similar to each other and were characterized by the following points: 1) the cyst wall typically consisted of three layers, namely, collagenous fibers, glia-like cells, and normal pineal cells; 2) the cyst wall was relatively thin, approximately 100 to 300 microns in thickness; and 3) deposits of calcification almost always existed on the side of the layer of collagenous fiber. Because these findings are clearly different from those previously reported, large benign cysts of the pineal gland, or at least some of them, may constitute a new pathological entity. It is important to consider this possible pathological diagnosis when dealing with pineal cysts.

Adult↗

Immunocytochemical analysis of the rat pineal gland using antisera generated against luteinizing hormone-releasing hormone (LHRH).

Seven different antisera generated against synthetic luteinizing hormone-releasing hormone (LHRH) were used to stain pineal gland and median eminence of the hypothalamus of normal rats. The LHRH immunogen complexes used to generate these antisera produced either N- or C-terminal directed antibodies or antisera that recognized both portions of the hormone molecule. Of these, four revealed LHRH-like immunoreactive material in the median eminence and pineal gland, two stained median eminence and not pineal, and one was positive in pineal only. These observations suggest that immunoreactive material in pineal gland may be an LHRH-like substance whose affinity characteristics are different from that of hypothalamic LHRH.

Animals↗

A direct neural projection from the intergeniculate leaflet of the lateral geniculate nucleus to the deep pineal gland of the rat, demonstrated with Phaseolus vulgaris leucoagglutinin.

The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into different subregions of the rat lateral geniculate nucleus. After a survival for 5-10 days, the rats were fixed by perfusion with 4% paraformaldehyde, whereafter the brains were cut in a cryostat and the tracer was localized by immunohistochemistry. After deposits of PHA-L involving the intergeniculate leaflet, a high number of PHA-L-immunoreactive fibers were observed to project directly into the posterior commissure. From the posterior commissure, some nerve fibers turned dorsally and entered into the deep pineal gland, a part of the pineal complex located in between the posterior and the habenular commissure. A few PHA-L-immunoreactive fibers were observed in the pineal stalk, but no fibers were detected in the superficial pineal gland. In cases where the injections were placed in the dorsal or ventral subnuclei, no immunoreactive nerve fibers were observed to enter the pineal complex. These results indicate that the intergeniculate leaflet of the lateral geniculate nucleus, a nucleus considered to be involved in circadian rhythmicity, might influence the pineal gland, via a neural projection to the rostral part of the pineal complex.

Animals↗

Characterization of the light response in the pineal gland of intact and sympathectomized rats.

Electrophysiological recordings were performed in the pineal gland of pigmented rats BD9 to investigate the possible contribution of a direct neural connection of the gland with the central nervous system in the transmission of photic information. Extracellular potentials were recorded during brief photic stimulation of the eyes before and after bilateral sympathectomy. Two types of responses could be distinguished in intact as well as in sympathectomized rats: spontaneously active units which were unresponsive to light flashes and units responding to photic stimulation with ON and ON/OFF discharges. Spectral sensitivity curves recorded from the pineal organ of dark adapted rats showed a maximum at 500 nm. Interruption of the sympathetic innervation by bilateral denervation or removal of the superior cervical ganglia did not alter the spectral properties of pineal units. Additionally, response-intensity curves and response threshold (about 0.0017 microW/cm2) were not changed after sympathectomy. These results suggest that the pineal gland of the rat receives projections from the visual system via a central pinealopetal innervation.

Action Potentials↗

The influence of lighting conditions upon the level and course of increase in specific activity of serotonin N-acetyltransferase in the developing chick pineal gland.

A diurnal cycle in level of serotonin acetyltransferase (acetyl-C0A:arylamine N-acety-transferase (EC 2.3.1.5) activity was found in the pineal gland of chicks aged 16 to 20 days maintained under lighting conditions. Diurnal variation in levels of activity was markedly reduced in the pineal gland of birds kept in constant darkness, and suppressed in the gland of chicks under constant illumination. High levels of activity attained during the dark phase of the normal cycle rapidly declined when the birds were transferred to the light. The light phase level of serotonin acetyltransferase of the pineal increased progressively from the 11th day of incubation to about 1 week post-hatch. This course of increase in enzyme activity was largely unaffected by lightning conditions. Under conditions for assay of serotonin acetyltransferase activity in the chick pineal gland and brain, radioactive serotonin gave rise to N-acetylserotonin, 5-hydroxy-indoleacetic acid and a further unidentified metabolite, which was quantitatively the major product.

Acetyltransferases↗

Protein gene product (PGP) 9.5 immunoreactivity in nerve fibres and pinealocytes of guinea-pig pineal gland: interrelationship with tyrosine- hydroxylase- and neuropeptide-Y-immunoreactive nerve fibres.

This light-microscopic (LM) immunohistochemical study has evaluated the presence and distribution of the pan-neural and neuroendocrine marker protein gene product (PGP) 9.5 in pinealocytes and nerve fibres of guinea-pig pineal gland. The pattern of PGP 9.5-immunoreactive (ir) nerve fibres has been compared with that of fibres staining for tyrosine hydroxylase (TH) or neuropeptide Y (NPY). The vast majority of pinealocytes stained for PGP 9.5, although with variable intensity. PGP 9.5 immunoreactivity was localized in pinealocytic cell bodies and processes. Double-immunofluorescence revealed that PGP 9.5 immunoreactivity was absent from glial cells identified with a monoclonal antibody against glial fibrillary acidic protein (GFAP). PGP 9.5 immunoreactivity was also present in a large number of nerve fibres and varicosities distributed throughout the pineal gland. The number of TH-ir and NPY-ir nerve fibres was lower compared with those containing PGP 9.5 immunoreactivity. All fibres staining for NPY also stained for TH. NPY-ir nerve fibres were found to be much more numerous than previously reported for this species. The double-immunofluorescence analysis indicated that almost all TH-ir nerve fibres of the pineal gland contained PGP 9.5 immunoreactivity. However, few PGP 9.5-ir nerve fibres, located in the periphery and the central part of the gland, were TH-negative. A large number of PGP 9.5-ir fibres was concentrated in the pineal stalk. In contrast, TH-ir and NPY-ir nerve fibres were rare in this part of the pineal gland. Our data provide evidence that immunohistochemistry for PGP 9.5 may be a useful tool further to differentiate central and peripheral origins of pineal innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of near-ultraviolet light on serotonin N-acetyltransferase activity in the chick pineal gland.

Effects of near-ultraviolet light (UV-A; 325-390 nm, peak at 365 nm) on the activity of the pineal serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) were examined in chicks. Acute exposure of dark-adapted animals to UV-A radiation produced a marked decline in NAT activity of the pineal gland. The magnitude of this suppression was dependent upon duration of the light pulse and the age of the animals. The decrease in the nighttime NAT activity evoked by a 5 min pulse of UV-A light applied during the fourth hour of the dark phase of the 12 hr light:12 hr dark cycle (LD) gradually deepened during the first 40 min after the return of animals to constant darkness, then the enzyme activity began to rise, reaching control values by 2 hr. Exposure of chicks to a 5 min pulse of UV-A light during the ninth hour of the dark phase produced a marked decline in pineal NAT activity, which was reversible after 15 min of darkness. Pretreatment of animals with an inhibitor of catecholamine synthesis, alpha-methyl-p-tyrosine (300 mg/kg, i.p.), or with a blocker of alpha2-adrenergic receptors, yohimbine (2 mg/kg, i.p.), antagonized the suppressive effect of UV-A light on nighttime NAT activity of the chick pineal gland. It is concluded that UV-A irradiation, similar to visible light, potently suppresses melatonin biosynthesis in the chick pineal gland, with an alpha2-noradrenergic signal playing the role of an intermediate in this action.

Animals↗

Postnatal development of the rabbit pineal gland. A light- and electron-microscopic study.

The development of the rabbit pineal gland has been studied by light and electron microscopy from the 1st to the 120th postnatal day. After 24 h of postnatal life, the pineal parenchyma is highly cellular, showing two identifiable cell types: pinealocytes I and II. Immature type II pinealocytes arrange either in cellular cords or clusters or forme rosette-like structures. At the 5th postnatal day, corticomedullar differentiation is established. Rosette-like structures and cellular cords are absent from the cortex. Along the postnatal period, nuclei of pinealocytes are set apart due to cytoplasmic widening and development of cell processes. These structures pervade the cellular cords and rosette-like structures formed by immature type II pinealocytes. Rosette-like structures are no longer seen beyond the 30th postnatal day, and cords of type II pinealocytes from the 90th postnatal day on. At this time, the rabbit pineal gland is considered to be histologically mature.

Animals↗

Estradiol modulation of pineal gland activity in the wild bandicoot rat, Bandicota bengalensis.

In the present study, the effect of estradiol dipropionate on the cytology and mitotic activity of the pineal gland was evaluated in adult ovariectomized and juvenile bandicoot rats, Bandicota bengalensis. Estradiol treatment for 5 days inhibited the ovariectomy-induced hypertrophy of the pineal gland, and increased the nuclear diameters of pinealocytes in juvenile males while having no effect on the pineal cytology of juvenile females. Estradiol injection induced mitosis in the pinealocytes of adult ovariectomized and juvenile bandicoot rats. Thus, estradiol exhibited a dual action (stimulatory and inhibitory) on the pineal gland of this wild rat.

Animals↗

Presynaptic and postsynaptic effects of neuropeptide Y in the rat pineal gland.

Neuropeptide Y is colocalized with noradrenaline in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC50 of 50 nM, the potassium-evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin-sensitive G protein-coupled neuropeptide Y-Y2 receptors and is independent from, but additive to, the alpha 2-adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC50 of 5 nM, the beta-adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y-Y1 receptors. This moderate neuropeptide Y-induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a beta-adrenergic stimulation. On the contrary, in the presence of 1 mM ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.

Animals↗

Degeneration activity of the pineal gland after sympathetic denervation.

After removal of the superior cervical ganglia the pineal gland of the rat showed a period of transient increase in activity of serotonin-N-acetyltransferase. This degeneration activity was preceded by a decline of the levels of endogenous noradrenaline and an impairment of the 3H-metaraminol uptake. Twenty-seven hours after sympathetic denervation the levels of the endogenous neurotransmitter were almost completely depleted, while either 24 h or 21 days after denervation total uptake of the tritiated amine decreased to only about 50% of the control values. Previous chronic sympathetic decentralization elicited in the pineal gland post-junctional supersensitivity, as judged by the enhanced degeneration activity observed in decentralized glands after sympathetic denervation. The present findings confirm that, in endocrine glands and similarly to other autonomically innervated organs, acute denervation induces degeneration activity.

Animals↗

Synaptic ribbons during postnatal development of the pineal gland in the golden hamster (Mesocricetus auratus).

Synaptic ribbons, functionally enigmatic structures of mammalian pinealocytes, were studied during the postnatal development of the pineal gland in the golden hamster (Mesocricetus auratus). On day 4 post partum, synaptic ribbons appear in cells that have already started to differentiate into pinealocytes. Between days 4 and 9, an increase in the number of synaptic ribbons occurs, concomitant with the continuing differentiation of the pineal tissue. Between days 9 and 16, when differentiation of this tissue is almost completed, the number of synaptic ribbons decreases and approaches that characteristic of the adult pineal gland. During development, the synaptic ribbons increase in length, and dense core vesicles are frequently found in the vicinity of these structures. It is assumed that a functional relationship exists between dense core vesicles and the synaptic ribbons, which are considered to be engaged in a certain form of secretory activity of the mammalian pineal gland.

Animals↗

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels.

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.

Animals↗

[Motilin-like immunoreactivity in the canine pituitary and pineal glands--a histochemical study].

Motilin-like immunoreactivity in the canine pituitary and pineal glands shown by radioimmunoassay was re-investigated by histochemistry using anti-porcine motilin sera. Immunostaining of duodenal Mo cells was examined as a control. Tissues were fixed in Bouin's fluid and embedded in paraffin. Sternberger's peroxidase anti-peroxidase method was employed for histochemical reaction. Three lots of anti-motilin sera raised in rabbits ( R1104 , R1105 , R1106 ) and one lot of anti-motilin serum raised in a guinea pig ( GP2803 ) were used. An absorption test of the immunohistochemical reaction was performed using motilin (Mo 1-22), N-terminal fragment (Mo 1-17), or C-terminal fragment (Mo 7-22). The results obtained were summarized as follows: In the pituitary gland, endocrine cells showing motilin-like immunoreactivity were localized in the pars distalis and pars intermedia. In the pineal gland, pinealocytes showed no motilin-like immunoreactivity. Pituitary endocrine cells were strongly stained with two lots of anti-motilin sera ( R1104 , R1105 ). No distinct reaction was demonstrated with two other anti-motilin sera ( R1106 , G2803 ). The minimum concentration of antigens required for absorption of the immunohistochemical reaction was determined by their doubling-dilution. When R1105 anti-serum (1:1000) was pre-incubated with Mo 1-22, immunostaining of duodenal Mo cells re-appeared at a concentration of 0.1 X 2(-8) g/l, whereas pituitary endocrine cells remained unstained at a concentration of 0.1 X 2(-10) g/l. Using Mo 7-22, immunostaining of pituitary endocrine cells was absorbed up to a concentration of 0.1 X 2(-14) g/l, whereas duodenal Mo cells were positively stained at a concentration of 0.1 X 10(-6) g/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Morphometry of the pineal gland in overweight individuals.

While obesity is an ever increasing problem in today's world, numerous facts suggest that its side-effects continue to be underestimated. Recent studies link obesity with pineal gland hormone and melatonin. The aim of this study was to determine differences in morphological attributes of the pineal gland in normal and overweight people in terms of pineal width and volume. A lower pineal width and volume in overweight individuals stated in the study may suggest a different excretory activity of the pineal gland.

Adolescent↗

Cytophysiological responses of the pineal gland to intermale aggression in a wild rat.

Intermale aggression by pairing bandicoot rats (Bandicota bengalensis) in their home cage, continuously for three hours, stimulated the pineal gland activity, cytologically measured by decreasing cell population density and increasing nuclear size of the pinealocytes, in the socially subordinate animals. The pineal gland of the dominant animal was not perceptibly affected by aggression. It is suggested that during aggression, the subordinate rats perhaps suffered from psychosocial stress that might have caused hyperactivity of their pineal gland.

Aggression↗

Diurnal changes of GABA turnover rate in brain and pineal gland of Syrian hamsters.

Circadian rhythms of GABA turnover rate in cerebral cortex, preoptic area-medial basal hypothalamus (PMBH), cerebellum, and pineal gland were examined in Syrian hamsters kept for 3 months under either long (14 h of light/day) or short days (10 h of light/day). In vivo GABA turnover rate was measured by the increase of GABA levels following inhibition of GABA-transaminase by gamma-acetylenic GABA. Under long photoperiods, a significant rhythm of GABA turnover was detected in the four areas studied (cerebral cortex, PMBH, cerebellum, and pineal gland), with maxima at night. A Cosinor analysis indicated acrophases which varied from 2300 to 0400 h (3rd to 8th h of darkness). Under short photoperiods, there were no significant circadian variations in GABA turnover in the cerebral cortex, and the synchronization in turnover rate among the remaining regions was lost, with acrophases being detectable either during the light phase of daily photoperiod (PMBH) or at night (cerebellum, pineal gland). Steady state levels of GABA also changed periodically in the same brain regions under both lighting environments, although phase relationships of circadian rhythms in GABA content and turnover rate varied significantly among tissues, as well as on photoperiodic conditions.

Animals↗