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PubMed1980

Increased adrenaline, beta-adrenoreceptor stimulation and phospholipid methylation in pineal gland of spontaneously hypertensive rats.

1. In pineal glands of adult spontaneously hypertensive rats (Okamoto strain), dopamine levels increased 34%, adrenaline concentrations increased 152% and noradrenaline levels decreased by 26%, when compared with Wistar-Kyoto normotensive controls. 2. These results are consistent with the hypothesis of an increased uptake of peripheral adrenaline resulting in increased release of noradrenaline from pineal sympathetic nerves in hypertensive rats. 3. The activity of pineal N-acetyltransferase was increased fourfold in hypertensive rats, indicating increased stimulation of pineal beta-adrenoreceptors. 4. Methylation of pineal membrane phospholipids was also increased (100-320%) in hypertensive rats. 5. These results indicate a correlation in vivo between increased beta-adrenoreceptor stimulation and increased methylation of membrane phospholipids in the rat pineal gland, which could result in changes in membrane fluidity and affect the coupling of the beta-adrenoreceptors to the adenylate cyclase.

Acetyltransferases↗

PubMed1989

Differential control of tryptophan hydroxylase expression in raphe and in pineal gland: evidence for a role of translation efficiency.

In a previous study, we characterized two tryptophan hydroxylase mRNAs (TPH mRNAs) in the pineal gland. However, we failed to detect these species in the raphe by Northern blot experiments. Here, we report by S1 nuclease analysis and in situ hybridization that these two TPH mRNAs, as well as a third species, are expressed both in pineal gland and in raphe. In both tissues, the three mRNAs are transcribed predominantly from the same promoter. Strikingly, from the results of S1 maping analysis, it was observed that the total level of TPH mRNA per tissue is at least 150 times lower in the raphe than in the pineal gland. In contrast, TPH antigen as quantified by immunoblot experiments is about threefold more abundant per raphe than per pineal gland. TPH mRNA from one raphe and one pineal gland yield in vitro about the same amount of TPH antigen, suggesting that the discrepancy in the ratios of TPH mRNA and TPH antigen between the raphe and the pineal gland results, at least in part, from a difference in the translation efficiency of TPH mRNAs in the two structures.

Animals↗

PubMed1990

Characterization of D1 dopamine receptors in the bovine pineal gland with [3H]SCH 23390.

Previous studies from this laboratory have shown that bovine pineal glands not only contain D2 dopamine receptors, but also that dopamine has dual effects on the activity of pineal serotonin N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM. We report here that the bovine pineal gland also possesses D1 dopamine receptors, which were characterized by using [3H]SCH 23390, the selective D1 dopamine receptor antagonist. SCH 23390 bound to bovine pineal membranes in a stereoselective, saturable and reversible manner. The receptor density (Bmax) was 974 fmol/mg protein and the dissociation constant (KD), as determined by saturation studies, was 0.56 nM, which is in good agreement with the KD calculated from kinetic studies (0.40 nM). Dopaminergic receptor agonists and antagonists inhibited [3H]SCH 23390 binding in a concentration-dependent and stereoselective fashion, demonstrating a pharmacology characteristic of D1 dopamine receptors. On the other hand, serotonin and serotonin receptor antagonists had a very low potency in inhibiting [3H]SCH 23390 binding. Studies involving dopamine receptor agonists revealed a low density, high affinity binding site (10%) and a high density, low affinity binding site (90%) in the bovine pineal gland. The results of this study are interpreted to indicate that the effects of dopamine in the pineal gland are modulated through mechanisms that involve both D1 and D2 dopamine receptors.

Animals↗

PubMed1983

Postnatal development of cell types in the rat pineal gland.

The morphological development of the rat pineal gland has been studied from 1 to 60 days of age. During the first days, undifferentiated cells (pinealoblasts) with scanty cytoplasm and frequent mitotic figures were observed. The differentiation of cell types (Types I and II pinealocytes) began on the third day after birth and was completed by days 15-20. At 3 days of age, nerve fibres were first observed, both in the connective spaces and in the parenchyma. After 5 days, an important hypertrophy of pinealocytes began, mostly Type I, which continued until 60 days of age. After 45 days, all the ultrastructural features described in the adult pineal gland were already present. The findings are discussed.

Animals↗

PubMedDate not supplied

Enhanced high-resolution sagittal MRI of normal pineal glands.

OBJECTIVE: Our goal was to determine the appearance and enhancement pattern of human pineal glands on MRI. MATERIALS AND METHODS: High-resolution sagittal MR images (3 mm section thickness with an 18 cm field of view) obtained in 60 patients were retrospectively analyzed to determine the size and enhancement patterns of normal pineal glands following the intravenous injection of contrast medium. RESULTS: Pineal glands were either solid (40%) or cystic (60%) with various enhancement patterns: diffuse (15%) and partially enhanced (25%) in solid and ring-like (20%) and peripherally partial (40%) in cystic. Their diameter exceeded 10 mm but was < 20 mm in five cases and resembled cystic pineal neoplasms. Two such cases were found to be histologically normal. CONCLUSION: Information on the appearance and enhancement patterns of normal pineal glands on MR images can improve the accuracy of diagnosing space-occupying lesions in the pineal region and perhaps help to prevent unnecessary surgery.

Adolescent↗

PubMedDate not supplied

Cholinergic innervation and function in the mammalian pineal gland.

Besides the noradrenergic sympathetic system originating from the superior cervical ganglion, a cholinergic innervation of the mammalian pineal gland has been studied over the past three decades. In 1961, it was shown that lesion of the parasympathetic greater superficial petrosal nerve of the monkey resulted in degeneration of nerve fibers in the pineal gland. This was supported by ultrastructural studies of nerve terminals within the pineal gland, demonstrating the presence of cholinergic terminals containing small clear transmitter vesicles. Biochemical studies further showed the presence of the enzyme acetylcholinesterase in several mammalian species. During the last decade, several advanced and more elaborate technologies have been developed, allowing pinealogists to establish the presence of cholinergic fibers and their receptors. Thus, choline acetyltransferase was shown in bovine pineal by immunohistochemistry. Muscarinic and nicotinic receptors were identified, characterized, and localized. Gene expression of receptors was visualized, and the receptor-mediated effector systems and functions were elucidated. Taken together, the present data suggest the presence of a cholinergic innervation of the mammalian pineal gland originating in peripheral parasympathetic ganglia. However, some of the neuronal projections to the pineal gland with origin in the brain (the central innervation) might also be cholinergic. The cholinergic nerve fibers enter the gland, where they are located both in the perivascular spaces and between the pinealocytes. Some of the terminals make synapses on pinealocytes or intrapineal neurons. The released acetylcholine from the terminals interacts with the receptors, then alters the cascade of receptor-mediated events, which results in decreased N-acetyltransferase enzyme activity, thus leading to decreased melatonin synthesis. This counterbalance mechanism between the sympathetic noradrenergic and the cholinergic systems maintains the homeostasis of pineal functions.

Acetylcholinesterase↗

PubMed1980

Embryonic carcinosarcoma (mixed tumour) of the pineal gland.

The present paper reports on a pineal gland tumour in an 8-year-old male child. Microscopic examination revealed a carcinomatous and a sarcomatous component. The aspect was characteristic of mixed embryonic carcino-sarcoma described in germ cell layer tumours of the gonads and kidney (Wilms' tumour). Ultrastructurally, the mixed character of the tumour was confirmed and also more differentiated elements were found differing from the appearances described in germ cell layer tumours. On the basis of the morphological examination it is concluded that at least in a proportion of the malignant mixed tumours of the pineal gland, their origin is to be found in the local neural elements and not the extraneural ones.

Brain Neoplasms↗

PubMed1994

Influence of lithium salts on chick pineal gland melatonin secretion.

Pineal melatonin secretion exhibits a rhythm which is identified as a circadian cycle with a period of between 20 and 28 h in most animals. The melatonin rhythm has an acrophase of about -30 degrees. The aim of this study was determine the effect of lithium on the melatonin rhythm since lithium is usually used as a therapeutic agent in manic-depressive disease. Lithium induced a delay of the melatonin acrophase which reached a value of about -45 degrees; lithium also produced another peak which had an acrophase at about +60 degrees. We speculate that lithium influences either inositol phosphate turnover or it merely changes the profile of the melatonin rhythm.

Animals↗

PubMed1989

Effects of electrical stimulation of the superior cervical ganglia on the number of "synaptic" ribbons and the activity of melatonin-forming enzymes in the rat pineal gland.

Melatonin metabolism in the mammalian pineal gland is under the clear influence of sympathetic fibers originating in the superior cervical ganglia (SCG). Previous studies suggested that pineal "synaptic" ribbons (SR) as well are regulated by the gland's sympathetic innervation. To gain more insight into the mechanisms involved, we examined the effects of sympathetic stimulation on SR number and on the activity of melatonin forming enzymes, serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). The SCG in adult male rats were stimulated electrically during daytime for either 15 or 120 min. Immediately following stimulation, the glands were removed and processed for electron microscopy and for the determination of NAT and HIOMT activities. No differences in pineal SR number, size or location were found in rats stimulated with either parameters when compared with sham-stimulated or control animals. While the activity of HIOMT remained unchanged, the activity of NAT was also unaltered following 15 min of stimulation, but was augmented approximately three-fold in animals stimulated for 120 min. It is concluded that if SR in the rat pineal gland are under sympathetic control, the regulation is different from that involved in melatonin formation.

Acetylserotonin O-Methyltransferase↗

PubMed1987

Noradrenergic stimulation of serotonin release from rat pineal glands in vitro.

The pharmacodynamics of serotonin (5-hydroxytryptamine; 5-HT) uptake and release were studied in rat pineal glands. Initially, uptake was tested by incubating pineals with several concentrations of [3H]5-HT. The incubation media also contained [14C]mannitol to which cells are impermeable. Since [14C]mannitol accumulates only in extracellular spaces, the radio-labelled sugar was used to determine the differential distribution of [3H]5-HT in pineal compartments. Intracellular accumulation of 3H in pineal glands increased linearly as a function of time for [3H]5-HT concentrations ranging from 1 to 10 mumol/l. The ratio of 3H to 14C also increased for the same time-interval, indicating that the glands accumulated [3H]5-HT preferentially in non-extracellular spaces. [3H]5-HT accumulated in pineal glands which were denervated for more than 7 days before testing, suggesting that uptake is not restricted to adrenergic terminals but also occurs in pinealocytes. In addition to uptake, spontaneous and noradrenaline-stimulated release of [3H]5-HT was tested in perifusion and/or step-transfer systems. Spontaneous release of [3H]5-HT was biphasic consisting of rapid and slower efflux phases. In contrast, release of [14C]mannitol was monophasic, characterized exclusively by rapid efflux. Since [14C]mannitol does not enter cells, the rapid and slower phases of [3H]5-HT efflux may represent release from pineal extracellular and intracellular compartments respectively. The identity of [3H]5-HT in pineal glands and perifusion media was confirmed by thin-layer chromatography. When L-noradrenaline was added to the perifusion media, [3H]5-HT efflux during the slower phase of release was significantly increased above the non-stimulated state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

Postnatal development of the pineal gland in the goat (Capra hircus)--light and electron microscopy studies.

This study was conducted to investigate structural transformations of the goat pineal gland during postnatal development. The pineals of newborn, 4-week-, 4-month-, 1-year- and 3-year-old male goats were prepared for qualitative and quantitative investigations at both light and transmission electron microscopy levels. In the first 4 months after birth, the pinealocytes developed very intensively, which was connected with enlargement of their volume as well as distinct qualitative and quantitative transformations of their cytoplasmic organelles. Parallel to these changes, the pineal parenchyma underwent deep reorganization and the mosaic pattern, characteristic for newborns, disappeared. At the same time the meshwork of blood vessels supporting the goat pineal gland developed conspicuously. From fourth months to one year of postnatal life continuation of the growth of some pinealocyte organelles and very intensive development of all components of the pineal connective tissue were observed. In the three-year-old goats some decrease in the relative volume of most cytoplasmic structures of pinealocytes as well as increase in collagen fibers in stroma were noticed. The investigations established intensive growth of the goat pineal to the age of 4 months, which included mainly some increase in the pinealocyte and their structures. The pineal gland of 4-month- and 1-year-old goats showed morphological features which are considered as symptoms of high secretory activity. The structure of the pineal gland in 3-year-old animals and the changes observed both in their pinealocytes and connective tissue in comparison with 1-year-old individuals point to some decrease in the goat pineal activity in this age.

Animals↗

PubMed1981

Evidence for existence of a serotonin N-acetyltransferase inactivating substance in rat pineal gland.

This study provides evidence for the existence of an inactivating substance in pineal glands, which may be responsible for the rapid inactivation of serotonin N-acetyltransferase seen in vivo and in vitro. This serotonin N-acetyltransferase inactivating substance enhances the thermal inactivation of the norepinephrine-stimulated serotonin N-acetyltransferase activity in rat pineal homogenate. Inactivation of serotonin N-acetyltransferase by the inactivating substance and the thermal inactivation of serotonin N-acetyltransferase at 37 degrees C exhibit the following identical properties. Both processes affect serotonin N-acetyltransferase without effect on other melatonin-related enzymes; can be blocked by addition of 0.5 mM [3H] acetyl CoA, but not coenzyme A in the preincubation mixture; and were unaffected by 0.1 M NaF or 4 mM beta-mercaptoethanol. These data are interpreted to suggest that protein dephosphorylation and disulfide exchange mechanisms are not involved in either inactivation processes. Unlike serotonin N-acetyltransferase, which is highly thermo labile, the inactivating substance is thermo stable at 37 degrees C for 40 minutes. In rat, the inactivating substance was found only in the pineal gland and was undetectable in other tissues. The inactivating substance is protein in nature, since it is not dialyzable but is inactivated by boiling or treatment with trypsin. The substance, which was able to inactivate serotonin N-acetyltransferase isolated from rate liver, exhibited no diurnal variation and its activity in rat pineal gland in culture was not influenced by norepinephrine. It is postulated that the interaction among acetyl coenzyme A, serotonin N-acetyltransferase and serotonin N-acetyltransferase inactivating substance may collectively regulate the synthesis of melatonin in pineal gland.

Acetyl Coenzyme A↗

PubMed1989

Melatonin content of the pineal gland in different mouse strains.

Pineal melatonin content at several times during the day and night was measured in 36 inbred strains of mice (Mus musculus) kept under LD 12:12 cycles. The results have indicated that only five inbred strains have pineal melatonin content, with higher levels during the night and lower levels during the day; the other 31 strains do not contain detectable melatonin in their pineal gland at any of times examined. The former group includes two commonly used strains (C3H/He and CBA/Ms) and three wild-derived strains (Mol-A, Mol-Nis, MOM). C3H and CBA mice showed a similar pattern of pineal melatonin rhythm with a peak at 2 hours before lights on. The peak levels were about 150 pg/gland in both strains. The rhythmic patterns of melatonin content in Mol-A, Mol-Nis, and MOM were slightly different from those in CBA and C3H. In the wild-derived strains, the peak of melatonin content did not occur at 2 hours before lights on but tended to occur at midnight. The peak levels were 67-91 pg/gland at the highest point in these strains.

Animals↗

PubMed1996

[Pineal functioning (melatonin levels) in healthy children of different ages. An update and the value of pineal gland study in pediatrics].

BACKGROUND: Classically, the function of the pineal gland involved the regulation of several endocrine and non-endocrine functions, such as seasonal breeding, biological rhythm synchronization and the sleep/wake cycle. The study of the pineal gland has not a new increasing interest due to the recent discovery that melatonin is the most potent antioxidant compound known to date. MATERIAL AND METHODS: We present here the data of aMT levels (mean +/- SD, pg/ml) measured by RIA in healthy children grouped by age and time of sample extraction. The group differences are evaluated by a mean comparison test. RESULTS: The results showed that plasma levels of aMT in cord blood reflect both the aMT levels and their circadian rhythm seen in the mother, without significant differences between umbilical artery and vein. In children between 18 months and 6 years of age, aMT concentrations at 09.00 reaches a maximum of 60.8 +/- 100.58. This value significantly decreased in children between 6-8 years old (35.54 +/- 9.17, p < 0.001), with a more significant decrease in children 8-13 years old (25.28 +/- 7.16, p < 0.01). However, in children 13-15 years of age, aMT concentrations increased to 31.14 +/- 8.29 pg/ml (p < 0.01). CONCLUSION: Our data support the existence of a functional pineal gland during the neonatal period, although it lacks the rhythmic secretion of aMT. From the preschool stage, children show a significant decrease in aMT concentration, except during the pubertal period when there is a small increase in aMT levels. In this paper we also review the available information about pineal function, specifically in regards to the relationship between pineal-melatonin and CURRENT PEDIATRICS in order to better understand the infant physiology and physiopathology related to this area.

Adolescent↗

PubMed1990

Induction of c-fos protein-like immunoreactivity in the rat and hamster pineal gland after the onset of darkness.

Induction of c-fos protein (FOS) after the onset of darkness was studied immunocytochemically in the rat and hamster pineal gland. The animals were kept on a 12:12 h light-dark cycle. Before the dark period no FOS staining was seen in either rat or hamster pineal cells. Five hours after the onset of darkness 342 +/- 18 pinealocytes/0.2 mm2 (mean +/- SD) displayed FOS-like immunoreactivity in the hamster pineal gland; in the rat pineal gland only 5 +/- 2 pinealocytes/0.2 mm2 showed a faint staining. Two hours later the density of FOS positive cells was decreased to 60 +/- 11/0.2 mm2 in the hamster but increased to 519 +/- 103/0.2 mm2 in the rat pineal gland. Three hours before the beginning of the light period no FOS positive cells were detected in either animal. Both the rat and hamster pineal gland showed a transient and temporally defined expression of c-fos protein in the middle of the dark period. This may be related to a more active functional state of pinealocytes, which is reflected in a peak of melatonin synthesis during the darkness.

Animals↗

PubMed1999

Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K and neuropeptide gamma.

Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K, and neuropeptide gamma. PEPTIDES 1999. Neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide gamma (NPG) are members of the family of tachykinins, and act preferentially on NK-2 tachykinin receptors. These peptides are widely distributed and are potent stimulators of smooth muscle contraction, especially in the respiratory and gastrointestinal tract. They also induce vasodilatation and plasma extravasation. Through their effects on the vascular tone, they are also potential regulators of the blood flow and therefore of the function of many organs and tissues. Tachykinins have been demonstrated to influence the secretory activity of endocrine cells, and they may have a physiological role as regulators of endocrine functions. A number of reports have indicated that NPK, NKA and NPG act on the hypothalamo-pituitary gonadal axis to regulate functions related to reproduction. Therefore, we thought that, at this point, it was important to review the available evidence suggesting the role of these tachykinins on reproductive functions by effects exerted at 3 different levels of regulation: the hypothalamus, the anterior pituitary and the gonads. These 3 tachykinin peptides were reported to have effects on reproductive functions, acting on the control of the secretion of gonadotropin and prolactin at the level of the hypothalamo-pituitary axis, and on the steroid secretion by the testes and the ovaries. Acting on the hypothalamus, tachykinins, mainly NPK, were reported to inhibit LH secretion, but this effect is dependent on the presence of gonadal steroids. On the anterior pituitary gland, however, tachykinins were shown to stimulate LH and prolactin secretion, and this effect is also dependent on the presence of gonadal steroids. Tachykinin concentrations in the hypothalamus and pituitary are regulated by steroid hormones. In the hypothalamus, estrogens and testosterone increase tachykinin concentration. In the anterior pituitary gland, estradiol and thyroid hormones markedly depress tachykinin concentrations. Ovariectomy and exposure to short photoperiods significantly increase anterior pituitary tachykinins in the Siberian hamster. In the pineal gland, SP and NK-1 receptors are present and, more recently, the presence of NKA and probably also NPK was demonstrated. Castration and steroid replacement modified the content of tachykinins in the pineal gland. The removal of the superior cervical ganglia was followed by an increase in NKA content in the pineal gland. These results suggest that gonadal steroids may influence tachykinins in the pineal gland. In the gonads, tachykinins stimulated the secretory activity of Sertoli cells, but inhibited testosterone secretion by Leydig cells. There are very few reports on the role of tachykinins in the ovary, but some of them indicated that these peptides are present in some of the ovarian structures, and they may affect the secretion of ovarian steroids. Thus, NKA, NPK and NPG appear to have a modulatory role, mainly acting as paracrine factors, on the hypothalamo-pituitary-gonadal axis.

Animals↗

PubMed1989

Xylamine enhances pineal gland N-acetyltransferase activity in vitro.

1. The action of N-2'-chloroethyl-N-ethyl-2-methyl benzylamine (xylamine) on rat pineal gland sympathetic innervation was examined. 2. This alkylating agent caused a concentration-dependent increase in pineal gland N-acetyltransferase (NAT) activity in neurologically intact pineal glands that was suppressed in glands previously subjected to bilateral superior cervical ganglionectomy. 3. Xylamine-induced elevations in NAT activity were attenuated by beta-noradrenergic antagonist drugs but not by alpha-noradrenergic antagonist drugs. 4. Since pineal gland uptake of radiolabelled norepinephrine (NE) was impaired by xylamine, the drug may increase pineal gland NAT activity by inhibiting NE reuptake into the presynaptic nerve terminal, thereby increasing the amount of the neurotransmitter available to stimulate pinealocyte beta-noradrenoceptors.

Acetyltransferases↗

PubMedDate not supplied

A median third eye: pineal gland retraces evolution of vertebrate photoreceptive organs.

In many vertebrates, the pineal gland serves as a photoreceptive neuroendocrine organ. Morphological and functional similarities between the pineal and retinal photoreceptor cells indicate their close evolutionary relationship, and hence the comparative studies on the pineal gland and the retina are the keys to deciphering the evolutionary traces of the vertebrate photoreceptive organs. Several studies have suggested common genetic and molecular mechanisms responsible for their similarities, but largely unknown are those underlying pineal-specific development and physiological functions. Recent studies have identified several cis-acting DNA elements that participate in transcriptional control of the pineal-specific genes. Genetic approaches in the zebrafish have also contributed to elucidating the genetic network regulating the pineal development and neurogenesis. These efforts toward elucidating the molecular instrumentation intrinsic to the pineal gland, back to back with those to the retina, should lead to a comprehensive understanding of the evolutionary history of the vertebrate photoreceptive structures. This article summarizes the current status of research on these topics.

Amino Acid Sequence↗