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Tumours occurring in the region of the pineal gland are uncommon in paediatric patients but may manifest with typical signs and symptoms. A 6-year-old boy with precocious puberty caused by a germinoma of the pineal gland detected on skull radiographs and confirmed on MR imaging is reported. The different types of tumours occurring in the region of the pineal gland and their imaging findings are discussed.
Pineal glands were grafted under the kidney capsule of mature male rats for periods of 20, 40, 60 and 100 days. Each grafted gland was then excised and divided into two halves. One half was processed for conventional electron microscopy and the other was fixed in aldehydes and then incubated in a zinc-iodide-osmium tetroxide mixture at pH 4.4 (A-ZIO-4.4). During the forty days following the operation pinealocytes showed the typical ultrastructural features associated with cells with a high protein and/or peptide secretory activity. On the other hand, during this period, the number of granular vesicles decreased progressively. From day 40 on, the grafted pinealocytes lacked granular vesicles. During the second half of the experimental period the ultrastructure of the pinealocytes indicated that their secretory activity was considerably decreased. During the acute phase of the experimental period numerous structures regarded as the tip of growing axons as well as typical nerve fibres appeared around blood vessels and within the paren chyma of the grafted gland. In the transplanted tissue obtained 60 and 100 days after the operation the growth cones were scarce, whereas typical nerve endings became numerous. These endings contained small clear vesicles which reacted positively when the tissue was treated with A-ZIO-4.4. The secretory activity of the grafted pineal gland and the nature of the nerve fibres which innervate the graft are discussed.
Leu-enkephalin-positive structures in the pig pineal gland were demonstrated immunohistochemically using mouse monoclonal antibody. The pineal glands were obtained from the newborn, 21-day and 7-month old female pig. The immunopositive nerve fibers were observed in the pineal gland as well as in the epithalamic areas. The leu-enkephalin-immunoreactive nerve fibers (single or forming small bundles) were localized mainly in the proximal part of the pineal and they were scarce in other parts. The localization of the fibers points to a central source of this innervation. The study did not show any age-dependent differences in the distribution and density of leu-ekephalin-positive nerve fibers.
The characterization and cellular localization of tryptophan hydroxylase mRNA in the human brainstem and pineal gland were investigated by using northern blot analysis and in situ hybridization histochemistry. Northern analysis of human pineal gland revealed the presence of two mRNA species that were absent in RNA isolated from human raphe. In situ hybridization experiments revealed very dense hybridization signal corresponding to tryptophan hydroxylase mRNA in cells throughout the pineal gland. In contrast, tryptophan hydroxylase mRNA was heterogeneously distributed in neurons in the dorsal and median raphe nuclei. Within the dorsal raphe, the ventrolateral and interfascicular subnuclei contained the greatest number of tryptophan hydroxylase mRNA-positive neurons. Also, the cellular concentration of tryptophan hydroxylase mRNA varied widely within the dorsal and median raphe. Comparison of the cellular concentration of tryptophan hydroxylase mRNA between the pineal gland and the raphe nuclei revealed an 11- and 46-fold greater average grain density of tryptophan hydroxylase mRNA positive cells in the pineal gland compared with the dorsal and median raphe, respectively. These findings are the first to demonstrate the cellular localization of tryptophan hydroxylase mRNA in the human brain and pineal gland as well as heterogeneity in the cellular concentration within and between these tissues.
The pineal gland via its secretory product, melatonin, influences the light-dark rhythm in most vertebrates including fish. Apart from the information concerning this circadian rhythm, the interrelation of the melatonin with other physiological processes has not been considered in fish. Thus, we evaluated the changes in the humoral innate immune system of seabream (Sparus aurata L.) and sea bass (Dicentrarchus labrax L.) specimens exposed to a constant light-dark photoperiod (12 hr L:12 hr D). Serum was obtained from blood samples collected at 02:00, 08:00 hr (light-on), 14:00, 20:00 hr (light-off) and at 08:00 hr again. Among the humoral innate immune responses, complement, lysozyme and peroxidase activities were determined. Complement activity was higher during the day than during the night in both fish species. Seabream lysozyme activity reached its maximum at 20:00 and 02:00 hr but was hardly affected in sea bass. Finally, the peroxidase activity of seabream was significantly higher at 08:00 hr than during the rest of the cycle while, in sea bass, it showed little variation. The present results demonstrate that the humoral innate immune system has a circadian rhythm based on the light-dark cycle and that this cycle might be affected by the pineal gland.
Study of the pineal gland of 91 Ungulates belonging to 55 species shows the constant presence of calcarine concretions of various importance. These concretions develop in the walls of vessels that first undergo a preliminary transformation characterized by the presence of alcian blue or PAS positive substances. In nearly all cases, the presence of alcian blue positive cells with processes (distinct from mastocytes) can be found in the pineal gland of ungulates. These elements sometimes contain fine calcarine granulations that probably are the site of origin of acervuli. These observations were extended to several marsupials, carnivora, pinnipeda and perissodactyles.
The goose pineal gland rhythmically produces two 5-methoxyindole compounds, namely melatonin and 5-methoxytryptophol. Melatonin concentrations were high at night and low during the day, while in contrast 5-methoxytryptophol levels were markedly higher during the day compared to the night-time values. Rhythmic oscillations in melatonin content, with high night-time values, have also been found in plasma and the retina of goose. The pineal and retinal melatonin rhythm mirrored oscillations in the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). Acute exposure of geese to light at night markedly decreased melatonin levels in the pineal, plasma, and retina. In addition, this light exposure resulted in a significant increase in pineal 5-methoxytryptophol content. Our results demonstrate, for the first time, the ability of the goose pineal gland and retina to synthesise melatonin and 5-methoxytryptophol in a rhythmic manner.
The present study assessed annual adrenal gland activity in the Indian tropical Jungle bush quail, Perdicula asiatica. We also elucidated the role of the annual variations in gonadal steroids and melatonin in the regulation of its activity. Increasing day length (photoperiod), ambient temperature and rainfall are positively correlated with adrenal and gonadal functions, and inversely related to pineal gland activity. Pineal, adrenal and gonadal weights showed cyclical patterns relative to environmental factors, which were also correlated with plasma melatonin, corticosterone and gonadal steroids, respectively. In both sexes of P. asiatica, pineal gland weight and/or plasma melatonin levels were inversely related to adrenal lipids, (e.g. phospholipids, free and esterified cholesterol) and plasma corticosterone levels. Melatonin levels also showed an inverse relationship with plasma testosterone and estradiol levels. These studies indicate that changes in environmental factors promote annual variations in adrenal and gonadal activity probably by modulating the pineal gland. Melatonin receptors have been localized in the pars tuberalis, adrenal gland and gonads of birds, the pineal gland may, therefore, mediate environmental stimuli indirectly and directly to down regulate adrenal and gonadal activity, which run in parallel in this species.
The pineal gland of the Japanese quail (Coturnix coturnix japonica) retained numerous follicular structures, each of which was composed mostly of pinealocytes and supporting cells radially arranged around the follicular lumen during the first 6 weeks of age. In the pinealocytes, paraboloids and regular stacks of lamellar disks, which were demonstrated at 1 day of age in a previous study [14], rapidly decreased in number after 1 week of age. From 1 to 6 weeks of age, the pinealocytes had more developed lamellar whorls in the follicular lumen with the increased numbers of mitochondria in their apical protrusions and synaptic ribbons in their basal processes. In addition to these photosensory elements, pigment-containing cells occasionally accumulated in the basal side of the follicular structure. Their pigment granules, which were considered as melanin, gradually became larger and more roundish in shape after 1 week of age. The histological elements associated with the secretory function of the quail pineal were dense-cored vesicles and lysosomes in the pinealocytes and dense bodies in the supporting cells. The synaptic ribbons and the dense-cored vesicles in the pinealocytes rapidly increased in number at 1 week of age, scarcely exhibiting distinct changes thereafter. Thus, it is clarified that the foregoing photosensory and secretory elements change during the post-hatching development. Furthermore, it is suggested that, in respect of these elements, the pineal gland of the quail assumes more active appearances than that of the chicken.
The effects of the pineal gland extract and blood serum on the activity of the UDP-GalNAc:GM3, N-acetylgalactosaminyltransferase (GM3:GalNAc-T) from chicken retina were studied. Both preparations have inhibitory capability on the enzyme activity. Two types of inhibitory capabilities were found: one is heat labile and decomposes UDP-GalNAc and another is heat stable. When the pineal gland extracts were prepared from light-exposed chickens, the inhibitory capability increased with respect to the extracts from dark-maintained animals; vice versa, blood serum from dark-maintained animals had higher heat-labile and heat-stable capabilities than that from light-exposed chickens. In in vitro experiments, no difference was found in the inhibitory capability of blood serum extracts from pinealectomized animals compared to control animals. In vivo labeling experiments with pinealectomized animals in either light or dark showed similar differences in the labeling of the optic tectum gangliosides as the normal animals.
In the mammalian pineal gland synaptic ribbons (SRs) are dynamic organelles of pinealocytes undergoing a day/night rhythm, with small numbers during daytime and significantly higher numbers at night, similar to the formation of the pineal hormone melatonin. Whereas the day/night rhythm of melatonin synthesis is adrenergically regulated, data on the adrenergic regulation of SR numbers in the rat pineal gland are at variance. While some authors have demonstrated that isoproterenol (ISO) stimulates SR numbers, others could not find any effect. To clarify the issue, we carried out identical experiments in two age groups. It was found that in male Sprague-Dawley rats, administration of the beta-adrenergic agonist ISO (2.5 or 10 mg/kg body weight) increased SR profile numbers in one age group (3 weeks), but not in the other (8 weeks). These findings resolve the apparent discrepancy reported in the literature, by showing that the response to ISO of SR profile numbers is apparently lost during postnatal differentiation of the pineal gland.
Pineal glands of various vertebrate species synthesize melatonin in a circadian rhythm generated by an endogenous pacemaker. The levels of melatonin and activity of serotonin N-acetyltransferase (AA-NAT: a penultimate and key regulatory enzyme in melatonin biosynthesis) are low during the light phase and high during the dark phase of any natural or imposed light-dark illumination cycle. The expression of AA-NAT gene in rat pineal gland is regulated by a photoneural system that acts through the adrenergic-cAMP-related mechanisms in pinealocytes. Concomitant stimulation by noradrenaline of beta 1- and alpha 1-adrenergic receptors, in a mechanism of "AND gate" activation, results in a large, 60-100-fold increase in intrapinealocyte cAMP level. The role of cAMP-dependent transcription factors CREB, ICER and Fra-2 in turning on and off the AA-NAT gene expression is discussed.
The pineal gland is part of the neuroendocrine system that modulates immune functions. Because the gland is outside the blood-brain barrier, it is accessible to direct feedback from circulating cytokines that affect the synthesis and secretion of melatonin. Recent studies have suggested that intrinsic immunoregulatory cytokines mediate these neuro-immune interactions under the control of sympathetic innervation to the pineal. This study focused on the expression of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6), two cytokines that have important regulatory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-beta1, but not IL-6, was expressed in freshly dissected rat pineal glands from neonatal age (1-day-old) into adults. Immunocytochemistry for TGF-beta1 in adult glands revealed localization of this protein in astrocyte-like cells. The sympathetic neurotransmitter norepinephrine (NE) increased transcript levels for both TGF-beta1 and IL-6 in adult pineal organ cultures. The effect of NE on IL-6 expression was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregulatory molecule interleukin-1beta (IL-1beta) up-regulated the expression of both IL-6 and TGF-beta1 in adult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF-beta1 and IL-6 have intrinsic regulatory roles in the pineal gland and that both neural and immune factors are important mechanisms of regulation.
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The activity of serotonin N-acetyltransferase, the key enzyme of melatonin synthesis, shows a marked circadian rhythm in the pineal glands of various animal species. The regulation mechanism of the N-acetyltransferse rhythm in birds is different from that in mammals. N-Acetyltransferase activity in rat pineal gland is controlled by the central nervous system through the sympathetic nerves from the superior cervical ganglion, while in chicken the endogenous oscillator for N-acetyltransferase rhythm is presumably located in the pineal gland. Recently it has been shown that N-acetyltransferase activity oscillates in a circadian manner in the organ culture of chicken pineal glands. When chicken pineal glands were organ-cultured under continuous illumination, the nocturnal increase of enzyme activity was suppressed. These observations suggested that chicken pineal gland contains a circadian oscillator, a photoreceptor and melatonin-synthesising machinery. A central question arises whether the circadian oscillation of N-acetyltransferase activity and its response to environmental lighting are generated within the cell or are emergent properties of interaction between different types of pineal cells. I report here that in the dispersed cell culture of chicken pineal gland, N-acetyltransferase activity exhibits a circadian rhythm and responds to environmental lighting in the same manner as in the organ culture.
The sexual dimorphism of the Harderian glands of golden hamsters is regulated by a complex interaction of the gonads and pineal gland. Ovariectomy was shown to prevent the conversion to male-type gland which normally follows blinding. Testosterone administration in combination with blinding and ovariectomy promoted the male type. Ovariectomy after 8 wk of blinding was ineffective in reversing the effects of blinding on the Harderian glands, but ovariectomy and pinealectomy caused complete reconversion to the female type. To our knowledge, this is the first report to demonstrate an influence of the ovaries on the Harderian gland of the hamster. In males, administration of testosterone for 7 days after 8 wk of castration was shown to have little effect on the conversion to the female type which normally attends castration, whereas testosterone injection followed by a period of blinding completely reversed the effects of castration on the Harderian gland. These studies, along with previously published reports, strongly suggest that the male-type Harderian gland is expressed whenever significant androgen levels are present, or when the glands are exposed to androgen priming during or just prior to a period of blinding-induced pineal activation. The probable role of ovarian androgens in mediating conversion to the male-type gland is discussed.
The ontogeny of beta-adrenergic receptors was investigated in the pineal glands of rats 1-64 days of age. The density of beta-receptors increased about 3-fold between 1 and 16 days of age and decreased slightly by 64 days, correlating temporally with the development of the sensitivity of adenylate cyclase to norepinephrine in pineal gland. Preventing adrenergic innervation of the pineal gland by neonatal ganglionectomy or decentralization failed to prevent the development of beta-adrenergic receptors in pineal gland. Bilateral adrenal demedullation alone or in combination with ganglionectomy also failed to prevent the normal developmental increase of beta-receptors in the gland. These results, showing that the ontogeny of pineal beta-receptors correlated temporally with that of the responsiveness of adenylate cyclase to adrenergic neurohormones, support the hypothesis that the responsiveness of tissues ot beta-agonists is dependent on the development of the beta-receptor. In addition, these experiments show that the beta-adrenergic receptor can develop even in the absence of sympathetic innervation or circulating catecholamines produced by the adrenal medullae.
N-Acetyltransferase activity (NAT) exhibits a circadian rhythm in the pineal gland and retinas of chickens and is responsible for melatonin circadian rhythms. Chick pineal gland NAT was measured in vivo and/or in vitro after light-dark cycles and after pretreatments with short photoperiod, long photoperiod, and constant light. Prior lighting changed the shape (phase, amplitude, and duration) of the rhythm in vivo. Some of the alterations are "programmed" into the pineal gland because they were observed in vitro in pineal glands from chicks similarly exposed to lighting pretreatments.