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Cultured pineal ependymal cells from rat fetuses release into their incubation media immunoreactive neurophysin. The presence of neurophysin was assessed by radioimmunoassay. The culture medium was found to contain 440 pg neurophysin per mg protein.
The pineal has undergone marked changes as vertebrates have evolved from amphibians to mammals. The amphibian pineal is a photoreceptive organ which sends nervous information to the brain via pineal nerves: the mammalian and avian pineal have no direct connections to the CNS and their metabolism is controlled by an indirect pathway involving their peripheral sympathetic nerves. In addition, the pinealocytes of some birds also function as photoendocrine transducers, i.e., they convert a photic input reaching them directly through the skull into a hormone output. Through the secretion of melatonin and of some as yet undefined low molecular weight peptides, the pineal participates in the control of other neuroendocrine rhythms such as seasonal cycles in gonadal function.
OBJECTIVES: Pineal gland hormone, melatonin, is a current issue of interest for accumulating data concerning its diverse physiological functions. The disturbances in melatonin secretion are observed in different pathological conditions involving pineal regions, but it is not ascertained if those disturbances present any clinical implications. The aim of this work was to examine whether pineal gland compression changes melatonin secretion. SETTING AND DESIGN: The experiment was carried out on adult rats, divided into four equal groups: (i) control (no surgery was performed), (ii) sham-operated, (iii) with sham pineal gland compression and (iv) with pineal gland compression performed by cotton piece application. METHODS: The profile of melatonin secretion was assessed in blood samples collected five times daily, every second day, starting from 8 to 14 day following surgery. RESULTS: We found that surgery itself significantly increased night melatonin secretion in comparison to controls. By contrast, in pineal-gland compressed rats, melatonin secretion was lower than in control group, suggesting that the influence of pineal compression overcame that induced by operation stress. CONCLUSIONS: In conclusion, we presume that pineal gland compression (like in case of some tumors) results in decrease of the concentration of blood melatonin, that may possibly result in decreased protective action of the indoleamine.
115 pineal glands, collected from patients who died from various neurologic and visceral diseases, were studied. The Rosenthal fibres (RF) forming gliosis is consistently evident in the subependymal tissue around the gland, in the pineal recessus and in the intrapineal glial proliferation. In several instances the focal gliosis exhibited a central cystic degeneration. The RF-forming gliosis of the pineal gland appears independent of the basic diseases and of the process of atrophy and degeneration of the gland parenchyma. The embryonic development of the pineal gland could explain why the formation of RF may be considered a quasi-physiologic process of this region.
Extracellular potentials were recorded in the pineal gland of urethane-anesthetized rats. Two distinct populations of excitable pineal "cells" were found, the silent "cells" which were driven by habenula stimulation and the spontaneously active cells. In the former case 17 of the responses (median latency of 1.2 ms) showed a positive-negative potential, and 6 (about 1 ms latency) showed only positive potential of 1-2 ms duration. The remaining cells (114), which could not be driven by habenula stimulation, exhibited spontaneous activity with a firing frequency from less than 1 Hz to greater than 100 Hz with a median firing frequency of 10 Hz. These experiments clearly demonstrate a direct habenulo-pineal fiber pathway and furthermore show that there are neuronal elements in the pineal which are only activated by habenula stimulation.
PURPOSE: Pinealitis accompanying uveitis is well established in laboratory models of experimental autoimmune uveoretinitis. In naturally occurring uveitis, pinealitis has been demonstrated in the pineal gland from a mare with active uveitis and is suspected in some human uveitides. We have evaluated pineal glands from horses with various stages of uveitis for signs of immunopathology accompanying spontaneous uveitis. METHODS: Pineal glands from 10 horses with uveitis and from 13 horses without uveitis were evaluated for histochemical (H&E, collagen) and immunohistochemical (MHC class II antigen expression, infiltration of T and B lymphocytes, and glial fibrillary acidic protein (GFAP) and vimentin upregulation) evidence of inflammation. RESULTS: Septal areas of pineal glands from horses with uveitis had clusters of MHC class II antigen-expressing cells, T lymphocytes, and enhanced collagen deposition. These changes were not as readily observed in pineal glands from horses without uveitis. B lymphocytes were detected only in the pineal gland from the one mare with active uveitis in which T and B lymphocytes were organized into follicles. No differences in GFAP or vimentin immunoreactivity were noted in pineal glands from horses with or without uveitis. CONCLUSIONS: These pineal gland changes suggest that the pinealitis associated with equine uveitis is transient just as the uveitis of these horses is recurrent. Study of pineal glands from horses with clinically documented uveitis allows demonstration of subtle pineal changes associated with natural uveitis. Similar changes would be difficult to document in human patient populations.
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Numerous studies have tried to determine whether alterations in the hormonal content of the plasma would modify pineal function. Recent evidence has indicated that the pineal is relatively insensitive to alterations in plasma hormone concentration, as contrasted with the neuroendocrine hypothalamus which is very responsive to hormonal feedback. Therefore, two types of neuroendocrine glands appear to exist based on their ability to respond to hormonal feedback. The first type of neuroendocrine gland, exemplified by the neuroendocrine portion of the hypothalamus, is extremely sensitive to hormonal modulation and is concerned with maintaining the endogenous balance of plasma hormones. The second type of neuroendocrine gland, exemplified by the pineal gland, is principally responsible for converting its neural input, usually a environmental stimulus, into a hormonal messenger, irrespective of plasma hormone levels. These two types of neuroendocrine glands would act in synchrony to maintain homeostasis throughout a variety of external conditions.
In the mammalian pineal gland, serotonin (5-HT) is located both in the pinealocytes and in the noradrenergic nerve terminals. Pineal 5-HT can be metabolized by three different routes, one of these being its deamination, catalyzed by monoamine oxidase (MAO). MAO is known to exist as two isozymes, MAO-A and MAO-B. Using two different cytochemical methods at the ultrastructural level, we have localized the presence of MAO in the pineal gland of the rat. The use of selective inhibitors of A-type (clorgyline) and B-type (deprenyl) has shown that MAO-A is localized in the noradrenergic nerve terminals, while pinealocytes contain MAO-B. Taking into account that 5-HT is only deaminated by MAO-A, the specific association of each MAO isozyme with a defined cell type implicates that two cellular compartments are needed in the pineal gland for the biosynthesis of 5-methoxytryptophol and 5-methoxyindole acetic acid, while for the synthesis of melatonin and 5-methoxytryptamine just one cellular compartment, the pinealocyte, is appropriate.
Serial sections of pig pineal glands were stained with von Kossa's and Alizarin red S methods to determine the occurrence and localization of calcified concretions. In the pineal glands of pigs aged eight months, concretions were not found. A small number of concretions was observed in all investigated pineal glands of three years old pigs. The concretions were distributed in the connective tissue of the pineal capsule and septa. The potassium pyroantimonate method was used for ultracytochemical localization of calcium ions. In pinealocytes, precipitates were observed in nuclei, mitochondria, Golgi apparatus, endoplasmic reticulum and cytoplasmic matrix. Single precipitates were found on the outer membranes of dense bodies, multivesicular bodies and lysosomes. There were no differences in the amount or the localization of precipitates between dark and light pinealocytes and between pinealocytes of animals aged both eight months and three years. The results suggest that: (1) the calcified concretions in the pig pineal gland are formed by the leptomeningeal tissue without participation of the pinealocytes, (2) cytoplasmic dense bodies, specific components of the pig pineal gland, are only slightly involved in calcium turnover in the pinealocytes.
In the rat pineal gland, prominent expression of serine protease inhibitor 3 (SPI-3) mRNA is seen after systemic injection of lipopolysaccharide. The up-regulation of SPI-3 mRNA expression is also confirmed by northern blotting. Most SPI-3 mRNA-positive cells simultaneously express synaptophysin, a marker for pinealocytes, but not glial fibrillary acidic protein, a marker for astrocytes. This indicates that SPI-3 mRNA-positive cells are pinealocytes. Almost all SPI-3 mRNA-positive cells also showed translocation of the signal transducers and activators of transcription 3 (STAT3) into nuclei after lipopolysaccharide injection. These data support previous in vitro results that SPI-3 expression is induced in a STAT3-mediated manner. In addition, the expression of ciliary neurotrophic factor receptor (CNTFR) and leukemia inhibitory factor receptor (LIFR) mRNAs, but not of interleukin 6 receptor mRNA, was up-regulated after systemic lipopolysaccharide treatment. Because these receptors are upstream of STAT3, the present results suggest that cytokines such as LIF and/or CNTF induce SPI-3 expression via STAT3 in the pineal gland in response to inflammatory stimulus. We conclude that although the functional consequences of SPI-3 in the pineal gland during systemic inflammation are unknown, SPI-3 may have a crucial role in preventing some degenerative proteolysis induced by inflammatory stimuli.
The chick pineal gland contains histamine and tele-methylhistamine. The levels of both substances are elevated after treatment of chicks with the amino acid precursor of histamine, L-histidine (1 g/kg, ip). In control and L-histidine-loaded animals the pineal levels of histamine and tele-methylhistamine are higher in light-exposed than in dark-adapted animals (measured at the end of the light phase and in the middle of the dark phase of 12 hr light, 12 hr dark illumination cycle, respectively). The chick pineal gland contains histamine-immunofluorescent cells displaying mast cell morphology; they are seen in the vicinity of the capsule and in the parenchyma. Enzymatic studies showed the presence of the activity of histamine synthesizing and inactivating enzyme, i.e., L-histidine decarboxylase (HDC) and histamine-methyltransferase (HMT). The detected enzyme activities were sensitive to specific inhibitors of HDC (alpha-fluoromethylhistidine and alpha-hydrazinohistidine) and HMT (quinacrine and metoprine); inhibitors of aromatic amino acid decarboxylase alpha-methyl-DOPA and NSD-1015 were inactive on HDC. Exogenous histamine added to organ-cultured chick pineals strongly stimulated endogenous cyclic AMP accumulation and moderately increased melatonin secretion. The data, considered collectively, suggest that in avians histamine, probably originating from the pineal mast cell compartment, may function as a regulator of pineal gland activity.
Network analysis procedures have been applied to study the cell patterns on the dorso medial and ventral lateral formation of the inferior colliculus of different species, i-e: Cat, Tat and Monkey. The results suggests the existence of important interspecific differences, more particularly in the primates. These differences are more obvious in the dorso medial formation. The functionnal implications of these results are discussed.
Formation of the pineal gland hormone melatonin increases markedly at night in response to light-dark environmental alterations. Melatonin is synthesized from serotonin by an initial N-acetylation followed by methylation of the 5-hydroxy moiety by hydroxyindole-O-methyltransferase. Serotonin N-acetyltransferase (NAT; EC2.3.1.87), which catalyses the first reaction, is the rate-limiting enzyme in this process, and its activity increases dramatically with the onset of darkness. Because melatonin may play important biological roles in reproduction, ageing and sleep, understanding the molecular factors that regulate NAT is of particular importance. To identify proteins that regulate light-dark variations in pineal function, we used a subtractive hybridization technique based on the polymerase chain reaction (PCR) to isolate rat pineal gland messages that are differentially expressed by day and night. Here we report the molecular cloning of NAT and dramatic diurnal variations in its transcription. Independently, Klein and associates have cloned NAT from sheep pineal glands.
Pineal glands from 16 infants ranging from 38 weeks gestation to 3 years of age were fixed in buffered formalin; Paraffin sections were stained for neuron-specific enolase, glial fibrillary acidic protein, and S-100 protein (S-100) using the peroxidase-antiperoxidase method and hematoxylin and eosin, Masson-Fontana, and Bodian stains. The pineal glands of neonates consisted of cords of closely packed, dark, nucleated cells (type I) with intervening loosely arranged, large, clear cells (type II). The type I cells were frequently pigmented and occasionally exhibited rosette formation. They were positive for S-100 and negative for neuron-specific enolase. The type II cells were strongly positive for neuron-specific enolase and negative for melanin and S-100. The type I cells were the predominant cell type at birth; however, the number of type II cells gradually increased with age, and by the age of 1 year, only scattered S-100 positive cells, consistent with sustentacular cells, were found. The findings indicated that the human pineal glands undergo a remarkable morphologic and functional evolution as an endocrine organ in the postnatal life.
The human pineal gland and it anterior attachments were investigated grossly in the fresh state and microscopically in the sagittal plane and 25 degrees tangential to the coronal plane of sectioning. Fiber stains of tissue samples from the midline commissural attachments of the pineal gland indicated the presence of both myelinated and non-myelinated fibers connecting the pineal gland and the pre-tectal area. A previously unreported paired fiber tract was observed associated with the anterior inferio-ventro-lateral pineal gland. This paired tract appears to be physically separate and distinct from the posterior commissure. These tracts form a structural component of the wall of the pineal recess. The fibers coursing in this paired tract are myelinated, and are of two different sizes (1-3 microm diameter and 5-8 microm diameter) as determined by electron microscopy. Fibers from these tracts invade the pineal gland, and can be traced a short distance into the lateral pre-tectal area. The precise point of origin and termination for this paired tract is unknown.
The objective of this study was to determine the role of alpha-adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 microM) or the beta-adrenoceptor agonist orciprenaline (2-10 microM) increased the glands' production of melatonin. The time courses of melatonin production in response to these agonists were unaffected by the rats' pretreatment in vivo with the alpha-adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that had had their superior cervical ganglia removed were primed with either orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p) 1 hr before decapitation. Exposure of the pineal glands from these rats to orciprenaline evoked melatonin release that was similar in each group. These results lend weight to the suggestion that the marked potentiation by alpha-adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by beta-adrenoceptor agonists, demonstrated most readily in cultured glands or dispersed rat pinealocytes, does not carry over into significant augmentation of melatonin production in intact pineal glands.
The mammalian pineal organ is a major endocrine component of the circadian timing system, primarily concerned with the regulation of photoperiodic responses. The effect of different photoperiods on the diurnal variation in the concentration of melatonin and 5-methoxytryptophol (5-ML) was studied in the pineal glands, obtained at autopsy, of 38 human subjects, and measured by radioimmunoassay. A diurnal rhythm in pineal melatonin was evident only in the long photoperiod (April-September) with melatonin concentrations being 4.2 times higher at night (22.00-10.00 h) than during the day (10.00-22.00 h). In contrast, diurnal variations in the pineal 5-ML content were only observed in the short photoperiod (October-March) with high concentrations during day-time and low concentrations during night-time. In general, night-time concentrations of both melatonin and 5-ML were higher in summer than in winter. These data suggest that the synthesis of indoleamines in the human pineal exhibits a diurnal rhythm which is affected by seasonal changes in day length.