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The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review.

BACKGROUND: The growing teratoma syndrome is a recognized complication of metastatic nonseminomatous germ cell tumors of the testis and is managed surgically. It may also occur in intracranial nongerminomatous germ cell tumors. METHODS: The authors performed an English language computer search using the EMBASE data base (from January 1980 to December 1996) for pineal tumors, read all abstracts, and then selected all articles pertaining to germ cell tumors at this site. RESULTS: The case history of a 19-year-old male who presented with a pineal nongerminomatous germ cell tumor, which was treated with chemotherapy, is reported. Despite normalization of raised tumor marker levels, the pineal mass enlarged during chemotherapy. This was excised and proved to be a mature teratoma. A review of the literature regarding this complication of intracranial germ cell tumors is also presented. CONCLUSIONS: The authors believe this to be the first reported case of growing teratoma syndrome in the pineal gland of an adult patient, two previously reported cases occurred in children. The authors conclude that the pineal gland is an unusual but important site in which to recognize the growing teratoma syndrome.

Adult↗

Expression of tranferrin receptors in the pineal gland of postnatal and adult rats and its alteration in hypoxia and melatonin treatment.

Transferrin receptors (Tfrc) are membrane bound glycoproteins which function to mediate cellular uptake of iron from transferrin. We examined expression of Tfrc in the pineal gland of rats of different ages from 1 day to 12 weeks. The mRNA and protein expression of Tfrc increased up to 6 weeks of age and decreased in 12 week rats. Tfrc immunoreactivity was observed on pinealocytes and macrophages/microglia. By immunoelectron microscopy, the immunoreaction in pinealocytes was observed in the cytosol, on mitochondria and plasma membrane whereas in macrophages/microglia it was localized on the plasma membrane in 1-day to 2-week old rats. In older rats, the immunoreaction product in pinealocytes was associated with the plasma membrane and mitochondria only. Iron localization was observed in pinealocytes as well as macrophages/microglia. It is suggested that Tfrc are required for uptake of iron for cell proliferation and maturation in the pineal gland upto 6 weeks of age. The significance of Tfrc expression on mitochondria is speculative. They may be involved in iron transport to the mitochondria or for regulation of the secretory activity of pinealocytes. The TfrcmRNA and protein expression increased significantly in response to hypoxia in 12-week rats and this coincided with intense iron staining of the pinealocytes and macrophages/microglia. It is concluded that increased expression of Tfrc in response to hypoxia leads to excess cellular uptake of iron which may be damaging to the cells. Melatonin administration in hypoxic rats may prove to be beneficial as it reduced the Tfrc expression.

Aging↗

Normal patterns of melatonin levels in the pineal gland and body fluids of humans and experimental animals.

The normal 24 hours patterns of melatonin were described in experimental animals and man. The rhythms are generated by neuronal activity originating in the suprachiasmatic nuclei of the hypothalamus; the activity of these nuclei are synchronized by the prevailing light:dark environment as perceived by the retinas. As a consequence of this synchronization, pineal melatonin levels are always high at night and low during the day, irrespective of whether the animal being studied is nocturnally or diurnally active. The rhythmic production of melatonin in the pineal gland is interrupted by the exposure of animals, or man, to light during the normal dark period. Several factors may change the 24 hours pattern of melatonin production. Because daylength changes throughout the year there are seasonal effects on the melatonin rhythm. Also, age is a major factor in determining the ability of the pineal gland to metabolize serotonin to melatonin. In advanced age pineal melatonin production is severely limited in both the human and in experimental animals. A variety of endocrine manipulations have been tested in terms of their impact on the ability of the pineal to produce melatonin. The majority of these have been rather innocuous although hypophysectomy does significantly curtail the synthesis of melatonin. To date, melatonin cycles have been usually described in rodents maintained under controlled environmental conditions in the laboratory; it can only be assumed that these rhythms are similar in animals in their natural habitat.

Aging↗

cAMP accumulation in the hypothalamus, cerebral cortex, pineal gland and brown fat across the wake-sleep cycle of the rat exposed to different ambient temperatures.

The concentration of adenosine 3':5' cyclic monophosphate (cAMP) was determined in the anteroventro-medial hypothalamus, the cerebral cortex, the pineal gland and the interscapular brown adipose tissue, during the different stages of the wake-sleep cycle of rats kept, under a 12-12-h light-dark cycle, in different environmental conditions, i.e., control (47-52 h at ambient temperature (Ta) 23 +/- 0.5 degrees C), exposure (47-52 h at Ta 0 +/- 1 degree C) and recovery (1-4 h at Ta 23 degrees C after 48 h at Ta 0 degree C). The results show that cAMP concentration consistently changed: (1) during the wake-sleep cycle in the anteroventro-medial hypothalamus, decreasing from wakefulness to sleep; (2) during the dark-light transition in the pineal gland, increasing with the onset of the light phase; and (3) with the environmental condition in the interscapular brown adipose tissue increasing, with respect to the control condition, in exposure and recovery. No significant changes in cAMP concentration were observed in the cerebral cortex.

Adipose Tissue, Brown↗

Participation of the pineal gland in sexual maturation of female rainbow trout (Oncorhynchus mykiss Walbaum).

In the study rainbow trout, pinealectomized at two different periods of their sexual cycle, i.e., at either 1 or 5 months before spawning, were studied. It was found that the lack of the pineal gland in the period directly preceding the spawning had no statistical effect on either spawning or the number of females that produced eggs. Pinealectomy performed during vitellogenesis delayed spawning by about 2 weeks and resulted in the absence of ovulation in 20% of the females. The results suggest that the pineal gland may influence the hypothalamo-pituitary-gonadal axis by altering the maturation period and controlling spawning in the rainbow trout.

Animals↗

Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures.

The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pineal gland free amino acids and indoles during postnatal development of the rat: correlations in individual glands.

Free amino acids and indoles were measured by HPLC in single pineal glands of 5-, 10- and 20-day-old rats sacrificed during mid-light and mid-dark at each age. Melatonin was detectable in neonates (5-day-old), but day vs night differences in indole constituents did not occur until 10 days of age. Free amino acid steady state levels were high in neonates and there was a tendency for reversal of day vs night differences coinciding with the onset of circadian rhythmicity in indole biosynthesis. High correlations (r greater than 0.85) existed for taurine vs. glutamate in individual glands regardless of age and time of sacrifice. These findings suggest that taurine and glutamate are biochemically interrelated and that developmental changes in amino acid metabolic pools reflect functional innervation of the gland.

Amino Acids↗

Lithium and rhythms of beta-adrenergic ([3H]CGP-12177) binding in intact rat retina, pineal gland, and hypothalamus.

A new assay technique for the determination of neurotransmitter binding in retinal fragments has been used to characterize and quantify beta-adrenergic receptors with the ligand [3H]CGP-12177. This assay allowed us to quantify beta-adrenergic receptors in the retina, pineal gland, and hypothalamus obtained from individual rats during a 10-hr period around the switch from light to dark under a 12-hr light/12-hr dark lighting cycle. A significant rhythm of beta-adrenergic binding was observed in the retina and pineal gland. These rhythms were abolished by chronic lithium treatment. In contrast to previous observations in whole brain preparations, lithium did not affect beta-adrenergic binding in brain tissue (hypothalamus) using this assay. Our data suggest that lithium may attenuate beta-adrenergic receptor down-regulation in pineal and retinal tissue. To the extent that this mechanism is important for the coding of information about light and dark in the environment, these observations might assist in our understanding of the clinical chronopharmacological properties reported for lithium.

Animals↗

Plurivesicular secretory processes and nerve endings in the pineal gland of the rat.

The pineal body of white normal rats, 1.5 to 3 months old, was studied under the electron microscope. A single type of parenchymal cell-the pinealocyte-is recognized as the main component of the tissue, and some of the structural characteristics of the nucleus and cytoplasm are described. The main morphological characteristic of the pinealocytes is represented by club-shaped perivascular expansions connected to the cell by thin pedicles. They are found lying in a large, clear space surrounding the blood capillaries. The name plurivesicular secretory processes is proposed, to emphasize the main structural feature and the probable function of these cellular expansions. A tubulofibrillar component is mainly found in the pedicle, and within the expansion there are numerous small mitochondria and densily packed vesicles of about 425 A. Two types of vesicles, one with a homogeneous content and another with a very dense osmium deposit, are described. Between the two types there are intermediary forms. In these processes, mitochondria show profound changes which may lead to complete vacuolization. The significance of this plurivesicular secretory component is discussed in the light of recent work on the biogenic amines of the pineal body and preliminary experiments showing the release of the vesicles containing dense granules after treatment with reserpine. These vesicles are interpreted as the site of storage of some of the biogenic amines. Bundles of unmyelinated nerve fibers and endings on large blood vessels which also contain a plurivesicular content are described and tentatively interpreted as adrenergic nerve terminals.

Animals↗

Influence of delta-sleep inducing peptide on melatonin synthesis in the rat pineal gland.

The influence of delta-sleep inducing peptide (DSIP) on rat pineal N-acetyltransferase (NAT) activity and melatonin levels was examined. Young adult rats received an injection of either saline or DSIP (either 15, 30 or 60 nmol/kg) at 20:00 h, immediately before lights out. DSIP at a dose of 15 nmol/kg significantly retarded the nighttime rise of pineal NAT activity and melatonin levels at 3 h into the dark phase. At the other two nocturnal time points (01:00 and 03:00 h) and the following morning (08:00 h) pineal NAT activity and melatonin levels were similar in all groups. The results confirmed a short-lived, dose-specific effect of DSIP on serotonin metabolism in the rat pineal gland.

Animals↗

Molecular mechanisms of neuroendocrine integration in the central nervous system: an approach through the study of the pineal gland and its innervating sympathetic pathway.

In the brain specialized cells known as 'neuroendocrine transducers' translate an input of neural activity into a hormonal output, e.g. oxytocin released into the blood stream. Other, more typical neurons make the reverse conversion constituting chemoreceptors which transform the hormonal 'language' into changes in their firing rate ('endocrine-neural' transduction). 'Endocrine-endocrine' transducing events occur at the level of the neurosecretory cells that translate a hormonal signal into another, different, hormone output. This article reviews the molecular aspects of several neuroendocrine integrative processes in the hypothalamus, the pineal gland and the cervical sympathetic pathway. The discussed results indicate that the pineal gland and its innervating sympathetic neurons located in the superior cervical ganglia constitute an easy-to-manipulate model system for the study of basic neuroendocrine mechanisms because: (i) receptors for various hormones exist in the mammalian pineal and sympathetic ganglia; (ii) the pattern of pineal steroid metabolism resembles that of the neuroendocrine hypothalamus; (iii) pineal estrophilic and androphilic receptors as well as the pattern of steroid metabolism are modulated by the sympathetic nerves; (iv) neuronal activity in the cervical sympathetic pathway is modified by hormone treatment at preganglionic, ganglionic and postganglionic sites.

Animals↗

Aicardi syndrome: an unusual case associated with pineal gland cyst and ventricular septal defect.

Aicardi syndrome is a cerebroretinal disorder consisting of a heterogeneous spectrum of clinical findings that includes the triad of infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae. This report describes a 6-month-old girl who has all of the essential features suggestive of Aicardi syndrome, as well as a pineal gland cyst and ventricular septal defect. Although the characteristic features of Aicardi syndrome have been described, its association with pineal gland cyst and ventricular septal defect has not been reported in the literature.

Agenesis of Corpus Callosum↗

Light microscopic analysis of cellular networks in the pineal gland of the golden hamster as revealed by methylene blue labeling.

Pineal glands of golden hamsters were stained transcardially with methylene blue and studied in paraffin sections by light microscopy. In the superficial portion of the pineal complexes, a selective labeling of a subpopulation of polymorphic cells with processes of different length was achieved. It could not be clarified, whether these cells form a syncytium or are only in contact with each other. Although functional interpretations of the morphological results have to be drawn with great care, the investigation might be of special interest for a better understanding of the well-known inhibiting effects of the dye to soluble guanylyl cyclase and nitric oxide synthase within this neuroendocrine gland.

Animals↗

Improved procedures for pineal gland fixation for electron microscopy.

The common procedures used for preparing some organs and tissues for electron microscopy, in which a fixative with the buffer portion adjusted to near-isotonicity to plasma is perfused in vivo, causes intolerable shrinkage of rat pineal cells. The present study was undertaken to optimize the parameters involved in the fixation of the pineal gland. The buffer and its concentration and the aldehyde or aldehydes used were among the variables investigated. The buffers tried were phosphate, cacodylate, PIPES, and HEPES. Decreasing the buffer concentration prevented shrinkage with all four buffers. The optimum concentrations were 0.05 M phosphate, 0.07 M cacodylate, 0.05 M or 0.057 M PIPES, and 0.1 M HEPES. PIPES and HEPES were clearly superior in retaining cytoplasmic density when compared with phosphate or cacodylate. The use of lithium PIPES and HEPES instead of the sodium equivalents enhanced membrane detail. A small volume of more concentrated aldehyde fixative perfused ahead of the main perfusate (a strong prewash) definitely helped prevent shrinkage. Using a mixture of aldehydes consisting of glutaraldehyde, formaldehyde, and acrolein reduced the tendency for shrinkage when compared with glutaraldehyde only. Some of the shrinkage space artefacts could be easily misinterpreted as normal features. Since the pineal gland commonly contains degenerating structures, a dependable fixation procedure is particularly needed. Also, accurate preservation is essential in the evaluation of physiological changes.

Animals↗

Local glucose utilization of the brain and pineal gland during stimulation of the cervical sympathetic trunk.

The quantitative autoradiographic 2-[14C]deoxyglucose method was employed to map the metabolic activity of the superior cervical ganglion and the entire brain during unilateral electrical stimulation of the cervical sympathetic trunk in the urethane-anesthetized rat. Stimulation of the cervical sympathetic trunk increased glucose utilization in the ipsilateral superior cervical ganglion (+95%) but did not produce side-to-side differences in glucose utilization in any of the brain structures examined in this study. Compared to the control nonstimulated animals, the rate of glucose metabolism in the pineal gland was increased 71% following stimulation of the cervical sympathetic trunk. The pineal gland was the only brain region out of 87 structures examined in which glucose utilization was increased by electrical stimulation of its sympathetic innervation.

Animals↗

Sarcoidosis of the pineal gland. Case report.

The authors report a case of sarcoidosis of the pineal gland with no other organ manifestation of the disease. The tumor was successfully removed by a direct surgical approach.

Adolescent↗

Nocturnal increase in the sensitivity of the Syrian hamster pineal gland to isoproterenol is darkness dependent.

The sensitivity of the Syrian hamster pineal gland to stimulation by isoproterenol is greatly increased in the latter half of the daily dark phase. This increased sensitivity requires a period of dark exposure for up to 6.5 hr. Also, if dark-maintained hamsters are exposed to light in the latter half of the night pineal melatonin levels drop precipitously but can be restimulated by isoproterenol administration. As the interval of light exposure continues, however, the pineal sensitivity to isoproterenol decreases.

Animals↗

Glutamate immunoreactivity is enriched over pinealocytes of the gerbil pineal gland.

Mammalian pinealocytes have been shown to contain synaptic-like microvesicles with putative secretory functions. As a first step to elucidate the possibility that pinealocyte microvesicles store messenger molecules, such as neuroactive amino acids, we have studied the distributional pattern of glutamate immunoreactivity in the pineal gland of the Mongolian gerbil (Meriones unguiculatus) at both light- and electron-microscopic levels. In semithin sections of plastic-embedded pineals, strong glutamate immunoreactivity could be detected in pinealocytes throughout the pineal gland. The density of glutamate immunolabeling in pinealocytes varied among individual cells and was mostly paralleled by the density of immunostaining for synaptophysin, a major integral membrane protein of synaptic and synaptic-like vesicles. Postembedding immunogold staining of ultrathin pineal sections revealed that gold particles were enriched over pinealocytes. In particular, a high degree of immunoreactivity was associated with accumulations of microvesicles that filled dilated process terminals of pinealocytes. A positive correlation between the number of gold particles and the packing density of microvesicles was found in three out of four process terminals analyzed. However, the level of glutamate immunoreactivity in pinealocyte process endings was lower than in presumed glutamatergic nerve terminals of the cerebellum and posterior pituitary. The present results provide some evidence for a microvesicular compartmentation of glutamate in pinealocytes. Our findings thus lend support to the hypothesis that glutamate serves as an intrapineal signal molecule of physiological relevance to the neuroendocrine functions of the gland.

Animals↗