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PubMed1987

Disturbed function of the pineal gland in familial amyloid polyneuropathy.

In order to estimate the function of the pineal gland, the sympathetic nervous system and the adrenal medulla in patients with familial amyloid polyneuropathy relative to healthy subjects, we have quantified urinary 6-hydroxymelatonin, normetanephrine and metanephrine. Urinary 6-hydroxymelatonin level correlated with neither of two O-methylated catecholamine levels in healthy subjects. The excretion of both 6-hydroxymelatonin and metanephrine were reduced in the patient group as compared with the control group, and the normal daily rhythm of 6-hydroxymelatonin was undetectable in the most of the patients. This finding indicates that the function of the pineal gland is disturbed in familial amyloid polyneuropathy.

Adrenal Medulla↗

PubMed1998

Postnatal developmental changes in NSE and NNE mRNA expression in the rat pineal gland: in situ hybridization histochemistry.

By in situ hybridization, neuron-specific enolase (NSE) and non-neuronal enolase (NNE) mRNAs were examined in the rat pineal gland at the postnatal developmental and adult stages. The distributions of hybridized signals were analyzed in comparison with immunohistochemical staining of synaptophysin (SYN), which is a marker for pinealocytes. In SYN-positive areas that were observed throughout postnatal developmental and adult stages, we detected both NSE and NNE signals, which increased simultaneously during early postnatal development and thereafter became stationary. Quantitative analysis revealed that NNE signals were 2- to 3-fold greater in number than NSE signals at any given stage. This predominant expression pattern of NNE differed from that in neurons, which usually showed both signals at similar levels and seemed to reflect the difference in physiological function from neurons. During the early postnatal stages, a cord-like arrangement of cells without distinct SYN staining was observed. This arrangement was the thickest at postnatal day 0 and became dispersed and thinner with development, showing a relationship with formation of vascularized connective tissue stroma. By in situ hybridization, many of the constituent cells showed weak NNE signals but no distinct NSE signals. However, some cells also showed weak NSE signals, suggesting heterogeneity of these cells. The characteristic NSE and NNE expression patterns in the pineal gland cells clarified in this study might provide a basis for further studies of the differentiation and function of the pineal gland.

Animals↗

PubMed1975

Effects of melatonin treatment and environmental lighting on the ultrastructural appearence, melatonin synthesis, norepinephrine turnover and microtubule protein content of the rat pineal gland.

Melatonin administration or exposure of rats to darkness for two weeks induced comparable changes in pineal ultrastructure, compatible with a generalized organ's activation. These include an increased number of ribosomes, procentrioles and microtubules, prominent nucleoli and Golgi apparatus, and annulate lamellae. Melatonin treatment resulted in a dose-dependent increase of hydroxyindole-O-methyl transferase and serotonin-N-acetyltransferase activities. In addition it increased by 85% the colchicine binding capacity of pineal homogenates, an estimation of the microtubule protein content of the gland. Pineal norepinephrine turnover was not affected by melatonin treatment. These data indicate that the pineal itself is a target organ for exogenously administered melatonin. Key words: Pineal gland, melatonin, norepinephrine, tubulin.

Acetylserotonin O-Methyltransferase↗

PubMed1981

Role of the pineal gland in male rats chronically exposed to increased temperature.

The effects of the pineal gland on endocrine function (especially those of the gonads) were investigated in male rats chronically exposed to increased temperature. Weanling male rats were either pinealectomized (Px) or sham-operated (Sh). Following one week of recovery, animals were assigned to either control temperature of 21 +/- 1 degree C (PxC and ShC) or a temperature of 35 +/- 1 degrees C (PxH and ShH). The animals were kept at their respective temperature for at least 30 days. In both groups (PxH and ShH) exposure to increased temperature resulted in a significant reduction in body and hypophysial weights, and in serum LH and testosterone levels as compared with the respective controls (PxC and ShC). Rectal temperature and serum corticosterone were also significantly increased. No changes were found in pineal hydroxyindole-O-methyltransferase activity of sham-operated rats kept in increased temperature (ShH vs. ShC). Pinealectomy alone (PxC vs. ShC) did not alter any of the measured parameters, except for increased pituitary LH content. Increased temperature plus pinealectomy (PxH vs. PxC; and PxH vs. ShH) caused a significant reduction in pituitary LH content and further accentuated (PxH vs. ShH) the diminished serum LH and testosterone levels evoked by exposure to high temperature. The results suggest that in male rats the pineal gland may play a role in moderating the changes in the reproductive processes that are induced by increased temperature.

Animals↗

PubMed1989

"Light" and "dark" pinealocytes of the porcine pineal gland.

Both qualitative and quantitative comparative studies of "dark" and "light" pinealocytes of the porcine pineal gland have been carried out. These cells differ from each other in their electronic density of cytoplasm, shape of nucleus, the structure of membrane bound dense bodies and the number of microtubules and smooth endoplasmic reticulum. The membrane bound dense bodies--characteristic structures of pig pinealocytes as well dense core vesicles occur in both types of cells. The relative volume of the majority of the cells' organellae apart from the Golgi apparatus, also do not show any significant difference. The results obtained support a functional basis for pinealocyte differentiation in the porcine pineal gland.

Animals↗

PubMed2005

Metallothionein-I-II expression in young and adult bovine pineal gland.

Aging is characterized, among other features, by an increased concentration of metal ions in the brain that may contribute to a greater increase in free radicals production. The present paper reports data regarding the concentration of some relevant metal ions (Cu, Fe, Mn, Zn), as well as the immunopositivity of metallothionein-I-II and GFAP in the bovine pineal gland with respect to animal aging. The pineal gland of young bovines displays several immunoreactive metallothionein-I-II positive elements in the parenchyma, whose number decreases with age. We also report that a well defined group of neurons bordering the third ventricle and located close to the subcommissural organ shows an intense metallothionein-I-II immunopositivity. The presence of metallothionein-I-II was confirmed by means of liquid chromatography coupled to tandem mass spectrometry. In particular, it proved possible to identify the amino acid sequences of the unique tryptic peptide not containing cysteine and two pepsin fragments containing cysteines. In conclusion, our data suggest the presence of a metallothionein-I-II expressing system in the pineal gland and ventricle-adjacent areas of the bovine epithalamus might possibly be related to the anti-aging effects of melatonin.

Aging↗

PubMed1982

Sympathetic regulation of circadian rhythm of serotonin N-acetyltransferase activity in pineal gland of infant rat.

The circadian rhythms of serotonin N-acetyltransferase activity in the pineal glands of infant and adult rats were compared. The nighttime increase of N-acetyltransferase activity in the pineals of infant rats was blocked by removal of superior cervical ganglion or by pretreatment with reserpine, l-propranolol, and cycloheximide. Injection of isoproterenol to infant rats markedly elevated pineal N-acetyltransferase activity. When the pineal glands of infant rats were organ-cultured, N-acetyltransferase activity spontaneously increased 7--12 h after the rats were killed. When infant rats were previously denervated or pretreated with reserpine and their pineals were cultured, this spontaneous elevation of N-acetyltransferase activity was abolished, indicating that the transient increase of the enzyme activity in organ culture was due to a liberation of catecholamine from degenerating nerve endings. Additional illumination until midnight prevented the nighttime increase of N-acetyltransferase activity in intact infant rats but not in blinded infant rats. These observations are taken to indicate that N-acetyltransferase rhythm in immature rat pineals is regulated by the sympathetic nerves in the same manner as in adult rat pineals, that the immature rat pineal does not contain a time-keeping system, and that there is no extraretinal light perception in infant rats as far as N-acetyltransferase rhythm is concerned.

Acetyltransferases↗

PubMed1987

Molecular mechanisms controlling norepinephrine-mediated release of serotonin from rat pineal glands.

This study describes various elements of the mechanism controlling norepinephrine (NE)-mediated release of serotonin (5HT) from rat pineal glands. After radiolabelling the endogenous pool of pineal 5HT with 3H-5HT, individual pineal glands were exposed to depolarizing buffers or those containing NE. Although 3H-5HT was not released by 50mM potassium, efflux of the indoleamine was increased by NE. Alpha-adrenergic receptors mediate the effects of NE as indicated by the fact that phenylephrine but not isoproterenol, a beta receptor agonist, also enhanced 3H-5HT release. This hypothesis is supported further by the fact that prazosin and phentolamine (alpha-antagonists) but not sotolal (beta-antagonist), inhibited the stimulatory effects of NE on 5HT release. In order to determine the intracellular second messenger involved in the 5HT release process, pineals were incubated with 8-bromo cAMP or the phorbol ester, PMA. PMA simulated the effects of NE and phenylephrine on 3H-5HT efflux, while cAMP had no effect. Furthermore, calcium-, phospholipid-dependent protein kinase activities in pineal homogenates were responsive to NE. These findings suggest that 5HT secretion from rat pinealocytes occurs rapidly in response to NE signals that act through alpha-adrenergic receptors in concert with phospholipid dependent protein kinase(s). These molecular processes are different from those involved in melatonin metabolism and may represent a general mechanism for regulating 5HT release in the brain.

Animals↗

PubMed1986

Effects of chemical and surgical ganglionectomy on electrical activity of the pineal gland of male rats.

In order to elucidate further the role of sympathetic innervation for pineal function, the influence of sympathectomy on the spontaneous electrical activity of single cells in the pineal gland of adult male rats was investigated. Extracellular single-unit recordings were made during nighttime in the pineal gland of urethane-anesthetized, blinded adult male rats that had been treated neonatally with 6-hydroxydopamine, or that were ganglionectomized either during, or 12-16 h or 36-40 h, prior to the recording experiment. These experiments revealed that the excitatory influence of the sympathetic system on pineal nocturnal electrical activity can be abolished by either chemical sympathectomy of neonatal rats or surgical superior cervical ganglionectomy in adult animals.

Animals↗

PubMed1999

The pineal gland and melatonin: molecular and pharmacologic regulation.

The pineal gland expresses a group of proteins essential for rhythmic melatonin production. This pineal-specific phenotype is the consequence of a temporally and specially controlled program of gene expression. Understanding of pineal circadian biology has been greatly facilitated in recent years by a number of molecular studies, including the cloning of N-acetyltransferase, the determination of the in vivo involvement of the cAMP-inducible early repressor in the regulation of N-acetyltransferase, and the identification of a pineal transcriptional regulatory element and its interaction with the cone-rod homeobox protein. Likewise, appreciation the physiological roles of melatonin has increased dramatically with the cloning and targeted knockout of melatonin receptors. With these molecular tools in hand, we can now address more specific questions about how and why melatonin is made in the pineal at night and about how it influences the rest of the body.

Animals↗

PubMed1975

A renin-like activity in pineal gland and hypophysis.

The presence and distribution of renin-like activity in hypophysis, pineal gland and some neural tissues were studies in both normal and salt-loaded rats. The Boucher micromethod was used to detect enzymatic activity. In normal rats both the pituitary and pineal glands contained significantly higher values of renin-like activity than did the other tissues examined. In salt-loaded animals there was a significant decrease of the renin-like activity of the glandular tissue while in the other brain areas the activity increased. The results are discussed in terms of the possible physiological role of the central renin-angiotensin system in the regulation of fluid and electrolyte balance.

Animals↗

PubMed1993

Brain-applied magnetic fields and immune response: role of the pineal gland.

In an attempt to clarify the mechanisms underlying immunopotentiation induced by prolonged exposure of the rat brain to static magnetic fields, and to evaluate the role of the pineal gland in that phenomenon, experiments were carried out on the following groups of adult rats (maintained under a 12 hr light/12 hr dark photoperiod): pinealectomized rats (Px); rats with micromagnets implanted to the occipito-parietal region of the skull (M); rats pinealectomized and implanted with micromagnets to the skull (PxM); sham-pinealectomized rats with non-magnetic beads implanted to the occipito-parietal area of the skull (ShPxMx); and intact controls (IC). Twenty-one days after surgery, animals of all groups were immunized with sheep red blood cells and tested for plaque forming cell (PFC) response and serum hemagglutinin level. Humoral immune reactions decreased significantly in Px rats, while increased markedly in M rats in comparison to the ShPxMx and IC controls. Compromised immune function induced by pinealectomy was restored by prolonged exposure of the brain to magnetic fields (PxM rats). Thus reconstituted immune responsiveness in PxM rats reached the level observed in controls, but was lower than that in M rats. The results imply that magnetic fields applied to the rat brain may exert their immunoenhancing activity in the absence of the pineal gland. However, this activity of magnetic fields is more pronounced in the presence of the pineal organ. The latter finding suggests the involvement of the pineal in the immunopotentiation induced by magnetic fields, but does not imply that magnetic fields operate solely via the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Postnatal development of female sheep pineal gland under natural inhibitory photoperiods: an immunocytochemical and physiological (melatonin concentration) study.

The purpose of this study was to determine structural and immunocytochemical changes taking place during the day and at night in developing sheep pineal gland under natural non-stimulatory photoperiods (summer solstice). Additionally, the diurnal cycle of plasma melatonin levels was charted and differences between diurnal and nocturnal pineal melatonin concentrations were analyzed. 36 ewes of three different ages were examined: infants (1-6 months old), pubertal and early fertile age (9-24 months old) and adults (36-60 months old). Plasma and pineal gland melatonin levels were higher in pubertal sheep than in infants or adults. Pubertal sheep pineal glands were also heavier, contained a larger number of pinealocytes and interstitial cells and displayed more evident innervation and vascularisation than infants or adults. There was no difference in the number of pinealocytes and interstitial cells between animals killed during daylight or at night. Gland weight, pinealocyte nuclear profile areas and plasma melatonin concentrations were all significantly higher at night than during the day.

Analysis of Variance↗

PubMed1987

Detection and high performance liquid chromatography identification of the summer rises of vasopressin and oxytocin immunoreactivity in the rat pineal gland.

The vasopressin (VP) and oxytocin (OT) contents of the rat pineal gland during the summer period were determined by RIAs. Both the levels of VP immunoreactivity and OT immunoreactivity rose markedly in August. The highest level of VP immunoreactivity occurred on August 6 [82 +/- 19 fmol/gland (+/- SEM)], compared to basal levels of 14 +/- 2 fmol/gland. Basal levels of OT immunoreactivity of 20 +/- 8 fmol/gland increased to a peak level of 193 +/- 72 fmol/gland on August 14. Analysis of immunoreactive components by HPLC demonstrated that rises were due to the peptides coeluting with authentic VP and OT, respectively. Levels of immunoreactive VP and OT in the hypothalamus, pituitary gland, and hippocampus did not show variation during the summer. The results show that the VP and OT content of the pineal gland is regulated in a tissue-specific fashion by seasonal influences.

Animals↗

PubMed2006

The pineal gland, but not melatonin, is associated with the termination of seasonal testicular activity in an annual reproductive cycle in roseringed parakeet Psittacula krameri.

The role of the pineal gland and its hormone melatonin in the regulation of annual testicular events was investigated for the first time in a psittacine bird, the roseringed parakeet (Psittacula krameri). Accordingly, the testicular responsiveness of the birds was evaluated following surgical pinealectomy with or without the exogenous administration of melatonin and the experimental manipulations of the endogenous levels of melatonin through exposing the birds to continuous illumination. An identical schedule was followed during the four reproductive phases, each characterizing a distinct testicular status in the annual cycle, namely, the phases of gametogenic quiescence (preparatory phase), seasonal recovery of gametogenesis (progressive phase), seasonal initiation of sperm formation (pre-breeding phase), and peak gametogenic activity (breeding phase). In each reproductive phase, the birds were subjected to various experimental conditions, and the effects were studied comparing the testicular conditions in the respective control birds. The study included germ cell profiles of the seminiferous tubules, the activities of steroidogenic enzymes 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and Delta(5)3beta-hydroxysteroid dehydrogenase (Delta(5)3beta- HSD) in the testis, and the serum levels of testosterone and melatonin. An analysis of the data reveals that the pineal gland and its hormone melatonin may play an inhibitory role in the development of the testis until the attainment of the seasonal peak in the annual reproductive cycle. However, in all probability, the termination of the seasonal activity of the testis or the initiation of testicular regression in the annual reproductive cycle appears to be the function of the pineal gland, but not of melatonin.

Animals↗

PubMed1980

Dihydroergocryptine binding sites in bovine and rat pineal glands.

High affinity binding of [3H]dihydroergocryptine (DHE) to crude membrane preparations of bovine and rat pineal glands was examined by a rapid filtration procedure through Whatman GFB paper. Scatchard analysis of bovine pineal membranes revealed a single population of binding sites with Kd = (4.8 +/- 1.9) X 10(-8) M (mean +/- S.E.M., n = 3) and binding site concentration = 834 +/- 103 fmol/mg of protein. When various alpha- and beta-adrenergic agonists or antagonists were tested for their ability to inhibit [3H]DHE binding the following Ki values (microM) were obtained: DHE (0.039), phentolamine (0.102), phenoxybenzamine (0.262), methysergide (0.670), L-epinephrine (2.27), serotonin (3.09), L-norepinephrine (3.20), octopamine (30.3), L-propranolol (1710), L-isoproterenol (greater than 2000). In order to obtain information on the pre- or postsynaptic location of pineal DHE binding sites, pineal 900 g supernatants were prepared from rats subjected to bilateral superior cervical ganglionectomy or sham-operation 7 days earlier. Ganglionectomy caused a 53% increase in the number of binding sites without changing significantly their Kd (5.2 X 10(-8) M and 5.5 X 10(-8) M in ganglionectomized and control rats, respectively). These results are compatible with the view that postsynaptic alpha-adrenoceptors are present in the pineal gland.

Animals↗

PubMed1996

Regional differences in the pineal gland of the cotton rat, Sigmodon hispidus: light microscopic, electron microscopic, and immunohistochemical observations.

Light microscopic, electron microscopic and immunohistochemical observations of the various portions of the pineal gland of the cotton rat (Sigmodon hispidus) were made. The volume of the proximal half occupied about 30% of the whole organ, and pinealocytes were slightly smaller in size in the proximal portion than elsewhere. The distal and intermediate portions contained few interstitial cells and numerous astrocytes, but the proximal portion lacked interstitial cells and had more abundant astrocytes than elsewhere. Astrocytes, which were immunoreactive for glial fibrillary acidic protein, mainly lined the pericapillary spaces in the distal and intermediate portions, but in the proximal portion these cells often surrounded isolated or groups of pinealocytes. In the distal and intermediate portions, abundant sympathetic fibers and less numerous non-sympathetic, peptidergic fibers were mainly localized in the pericapillary spaces; these fibers were sparsely distributed in the parenchyma close to interstitial cells or astrocytes. In the proximal portion, non-sympathetic fibers were scarce and sympathetic fibers were distributed abundantly and almost exclusively in the parenchyma. Most of the sympathetic fibers were adjacent to astrocytes and, occasionally, made specialized contact with them. Fenestrae in the capillary endothelium were numerous in the distal portion but absent in the proximal portion. Thus, marked differences in structure existed between the distal and proximal portions of the pineal gland of the cotton rat suggesting that both portions are functionally dissimilar. In addition, the present study indicates that the proximal portion of the cotton rat was well developed and showed morphological features similar to the deeply situated pineal glands of other mammals.

Animals↗

PubMed1993

Close microtopographical relationships between sympathetic nerve terminals and bulbous process endings of pinealocytes in the pineal gland of the Mongolian gerbil.

Previous studies have shown that pinealocytes of the gerbil pineal gland exhibit processes that form terminal swellings filled with abundant electron-lucent microvesicles. The membrane of these presumptive secretory microvesicles is known to contain synaptophysin, a major integral glycoprotein of neuronal synaptic vesicles. The present study was conducted to evaluate the microtopographical relationships between the vesicle-rich process swellings and intra-pineal nerve terminals. For this purpose, both nerve terminals and pinealocyte process endings were visualized immunohistochemically in the same semi-thin sections of plastic-embedded gerbil pineals, using antibodies directed against synaptophysin. This approach consistently revealed close spatial associations of punctate immunopositive nerve endings with intensity stained bulbous process terminals of pinealocytes in or near the perivascular spaces. The light-microscopic observations of intimate neuronal-pinealocytic relationships were corroborated at the electron-microscopic level. Perivascular varicosities with ultrastructural features characteristic of sympathetic nerve terminals were frequently juxtaposed to vesicle-filled process endings of pinealocytes. Analysis of serial thin sections showed that multiple point-to-point contacts are encountered between noradrenergic nerve terminals and pinealocytic process swellings. Our morphological findings imply that bulbous process terminals, at least in the gerbil pineal gland, are major targets for the neuronal control of the secretory activity of pinealocytes.

Animals↗