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PubMed1977

[The human pineal gland. Study performed on 747 glands].

The study of 747 human pineal glands shows that the weight of this organ is extremely variable. This weight shows seasonal variations. The weight of the pineal is identical in cancerous and non cancerous patients. It is lower (the difference being statistically highly significative) in a great majority of hepatic diseases. Microscopic study of 54 of these pineal glands (those obtained 2 to 6 hours after death) shows that the pineal concretions may have a variable origin: the vessel walls, the interlobular connective tissue, and certain pinealocytes that can then be colored by alcian blue.

Adolescent↗

PubMed1995

The pineal gland: photoreception and coupling of behavioral, metabolic, and cardiovascular circadian outputs.

Although removal of the pineal gland has been shown to have very little effect on the mammalian circadian system in constant darkness (DD), several recent reports have suggested that the mammalian pineal gland may be more important for circadian organization in nocturnal rodents than was previously believed. Removal of the pineal gland (PINX) facilitates the disruptive effects of constant bright light on wheel-running rhythmicity. This suggests at least two possibilities for the role of the pineal gland in the mammalian circadian system. First, pinealectomized rats may perceive ambient light intensity to be brighter than do sham-operated (SHAM) rats. Second, the pineal gland, probably via its secretion of melatonin, may also be involved in coupling components of the circadian system. Coupling, as we see it, may occur at several levels of organization: (1) between retinohypothalamic afferents and suprachiasmatic nuclei (SCN) oscillatory neurons, (2) among multiple SCN oscillators, (3) between the SCN and their multiple outputs, and/or (4) among the multiple circadian outputs themselves. In this study we show that PINX rats free-run with a longer period in four different light intensities than do SHAM rats. Moreover, the rate of increase of tau is greater among PINX rats than among SHAM rats. This supports the first hypothesis. We also show that in PINX rats the circadian rhythms of wheel running, general activity, body temperature, and heart rate are all more disrupted in constant bright light than are those of SHAM rats, and each rhythmic output is disrupted in parallel. This supports the second hypothesis. Melatonin is probably not involved in coupling presynaptic elements of SCN afferents in the retinohypothalamic tract to pacemaking cells within the SCN, since enucleation has no effect on SCN 2-[125I]iodomelatonin (IMEL) binding. Together the data do not discount either of the two hypotheses but do restrict the possible levels at which the pineal gland is involved in coupling. These data also further support a growing body of literature indicating that the pineal gland and its hormone melatonin play a role in mammalian circadian organization.

Animals↗

PubMed1994

The presence of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and preproVIP(111-122) in the mouse pineal gland.

A low to moderate number of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI)-immunoreactive nerve fibers with prominent boutons-en-passage were demonstrated in the pineal gland of the mouse. The two peptides, which are parts of the same precursor molecule, were distributed identically in the gland. Positive fibers were present in the connective tissue septae in the gland, in the pineal capsule, and in the pineal parenchyma. No VIP-PHI-immunoreactive elements were found in the deep pineal gland, in the pineal stalk, or in habenular and posterior commissures. This morphological distribution of immunoreactive nerve fibers, which is similar to the distribution in other mammals, indicates that the VIP/PHI fibers of the mouse pineal gland originate exclusively from perikarya in a peripheral ganglion, presumably one of the cholinergic ganglia of the head. No evidence for a VIPergic central innervation was found. VIP and PHI are connected via a bridging peptide equivalent to amino acids 111-122 of the precursor (preproVIP(111-122)). In order to demonstrate the possible existence of this peptide in intra-pineal nerve fibers, antisera directed against a synthetic sequence identical to preproVIP(111-122) and immunohistochemistry were applied. PreproVIP(111-122)-immunoreactive nerve fibers were observed in the mouse pineal gland, with the same distribution pattern and morphology as those immunoreactive for VIP and PHI. To quantify the peptide-immunoreactivities, 50 mice pineals were pooled, extracted, and the concentrations were measured radioimmunologically. The concentrations of the VIP and preproVIP(111-122) immunoreactivities were 1.7 and 2.0 pmol/g, respectively, whereas the concentration of PHI was 0.9 pmol/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Histamine-stimulated cyclic AMP formation in the chick pineal gland: role of protein kinase C.

The role of protein kinase C (PKC) in histamine (HA)-stimulated cyclic AMP formation in intact chick pineal glands was investigated. In the pineal gland of chick HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA potently increased cyclic AMP accumulation in a concentration-dependent manner. Treatment of intact glands with PKC inhibitors, i.e. chelerythrine and stautosporine, reduced the stimulatory effect of the HA-ergic compounds on cyclic AMP formation. HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA significantly increased inositol-1,4,5-trisphosphate (IP3) levels in intact chick pineal glands, indicating their activities on phospholipase C and 1,2-diacylglycerol formation. The stimulatory effect of HA on IP3 levels was antagonized by aminopotentidine, a potent blocker of H2-like HA receptors in avian pineal gland. Preincubation of chick pineal glands with a PKC activator, 4 beta-phorbol 12, 13-dibutyrate (4 beta-PDB), enhanced the accumulation of cyclic AMP elicited by HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA. On the other hand, 4 beta-phorbol, inactive on the PKC, was ineffective. Our results point to the possibility that PKC is involved in the regulation by HA of cyclic AMP synthesis in the pineal gland of chick. Furthermore, the cyclic AMP response to pineal HA receptor stimulation can be positively modulated by a concomitant activation of the PKC pathway.

Animals↗

PubMed1998

Light-dependent expression of pinopsin gene in chicken pineal gland.

The phase of a circadian clock in the chicken pineal gland is reset by an environmental light signal, which is captured by the pineal photoreceptive molecule(s). Here we show that the mRNA level of pinopsin, a predominant photoreceptive molecule in the pineal gland, undergoes a diurnal fluctuation in chickens maintained on a light/dark cycle. The mRNA levels in the light were approximately six times higher than those in the dark. This fluctuation was not observed in constant darkness, where the mRNA levels remained low. Subsequent light exposure of chickens increased the amount of pinopsin mRNA regardless of the circadian time. Clearly, the expression of pinopsin gene is controlled by a light signal, independent of the circadian clock. In vitro experiments using cultured pineal glands isolated from the visual system also revealed the light-dependent increase in pinopsin mRNA level, indicating that the pineal photoreceptive molecule(s) is responsible for the induction. These results demonstrate the presence of a feedback loop through which the light signal captured by pinopsin stimulates the transcription of its own gene in the chicken pineal gland. In contrast, pinopsin protein remained at an almost constant level in chickens maintained under the same light/dark cycles. The protein level, however, decreased to approximately 50% of the light/dark level under constant darkness and subsequently increased upon exposure to light after the dark period. It is suggested that, under the light/dark cycles, the pinopsin protein level is kept constant by the light-dependent synthesis, which would compensate for a possible degradation of pinopsin in the daytime.

Animals↗

PubMed1990

The pineal gland in newborn southern elephant seals, Mirounga leonina.

In the newborn southern elephant seal the pineal gland is very large, and both pineal and plasma melatonin concentration is elevated. The pineal gland was investigated during the first 24 h, and up to 20 days of age, in elephant seal pups. A primary aim of this investigation was to determine whether there are obvious ultrastructural characteristics of pinealocytes that are exhibiting extraordinarily high levels of activity. Blood and pineal glands were collected from thirty seven pups of known age which were sampled at random from early September to early November (1985) at Macquarie Island. The pineal gland is large (mean weight, 4.71 +/- 0.35 gm, range 1-9.3 gm) and actively secreting melatonin at birth. Melatonin concentrations were extremely variable, yet very high in pups during the first 24 h post-partum. Mean melatonin plasma concentration for pups 0-24 h was 17632.8 +/- 5723.8 pmol/l (4090.8 +/- 1327.9 pg/ml), ranging from 126 pmol/l (29 pg/ml) to 297000 pmol/l (68904 pg/ml). Electron microscopic examination did not reveal any marked changes in pinealocyte ultrastructure suggestive of increased secretory activity during this period. The large and extremely active pineal gland in newborn southern elephant seal suggests that it is actively involved in thermoregulation.

Aging↗

PubMedDate not supplied

Non-invasive evaluation of the effects of opening & closing of eyes, and of exposure to a minute light beam, as well as to electrical or magnetic field on the melatonin, serotonin, & other neuro-transmitters of human pineal gland representation areas & the heart.

Using the Bi-Digital O-Ring Test electromagnetic resonance phenomena between 2 identical substances, first the pineal gland representational (rep.) areas were localized on the 5 different locations on the surface of the head using microscope slides of the pineal gland or Melatonin (while the eyes are closed) as a reference control substance. The 3 pineal rep. areas along the mid-line of the head always showed two lobes connected as a "Dumbbell" shape, with one round or oval area at each side of the mid-line. From each side of the head, anterior and superior to the ear, it appeared in a shape resembling the side view of a pineal gland. When both eyes were open, Melatonin, Norepinephrine (NE), and Acetylcholine (ACh) markedly decreased, while Serotonin, Dopamine, and GABA increased significantly in the outer part of the pineal gland rep. areas. When both eyes were closed, Melatonin, NE and ACh increased markedly, with marked decrease in Serotonin, Dopamine and GABA in the outer part of the pineal gland rep. areas. However, in the inner core of the pineal gland rep. area, an opposite response was found. Thus, the pineal gland has 2 main lobes, and functionally each lobe seems to have two concentric areas with an inverse relationship, i.e., a "Functional Cortex" area and a "Functional Core" area. The biochemical changes between the cortex and the core are in an inverse relationship. Melatonin was also found in the S-A node & right side of normal heart when the eyes were closed. When the eyes were open, Melatonin was found in the left side of the heart, as well as the salivary glands, stomach, colon, etc. While both eyes were closed, when a weak light beam was exposed at different parts of the body, such as any part of the upper and lower extremities, Melatonin, NE, and ACh decreased, with an increase in Serotonin, GABA and Dopamine only in the functional cortices of the pineal gland lobes on the same side of the body. Even when both eyes were open, if a very weak narrow beam of light was exposed on any part of the body, Melatonin, NE and ACh decreased, while Serotonin, Dopamine and GABA increased compared with pre-exposure level in only the functional cortices of the pineal gland lobes in the same side of the light exposure, and the opposite effect was also observed in the functional core of the light exposed side only.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1979

Melatonin, the pineal gland and human puberty.

Animal experiments have suggested that the pineal gland produces an anti-gonadotropic hormone. The hamster, for example, undergoes reproductive collapse when kept in short-day periods, an effect which is abolished by pinealectomy. Although there is little direct evidence about the endocrine role of the pineal gland in man, it has been noted that tumours of the pineal gland in young boys are associated with precocious puberty and the human pineal gland has been suggested to produce a substance that holds sexual maturation in check. This observation has been extended by Kitay, who has shown that destructive tumours are associated with precocious puberty whereas hyperactive tumours are associated with delayed puberty. However, no studies have described any change of pineal function with normal puberty. Because two pineal indoles, melatonin and methoxytryptophol, have been shown to be antigonadotropic when administered to animals, we have now measured them in schoolchildren. Our findings show that in young boys there is an abrupt fall in the concentration of melatonin with advancing development suggesting that it may play an important physiological role in the control of human puberty.

Adolescent↗

PubMed1990

Innervation of the mink pineal gland with neuropeptide Y (NPY)-containing nerve fibers. An experimental immunohistochemical study.

An immunohistochemical investigation of the mink pineal gland was performed by use of antibodies raised in rabbits against neuropeptide Y (NPY) and Cys-NPY (32-36)-amide recognizing neuropeptide Y with an amidation at position 36 (NPYamide). NPY-immunoreactive nerve fibers were located predominantly in the rostral part of the pineal gland and in the pineal stalk. Immunoreactive nerve fibers were found throughout the pineal gland, but the number of fibers in the caudal part of the gland was low. The fibers were present both in the perivascular spaces and between the pinealocytes. Many NPY-immunoreactive fibers were also located in the posterior and habenular commissures; some of these fibers were connected with the fibers in the rostral part of the mink pineal gland, indicating that at least some of the NPY-immunoreactive nerve fibers are of central origin. The nerve fibers immunoreactive to amidated NPY were distributed in a similar manner. However, the number of fibers immunoreactive to NPYamide was lower than the number of fibers immunoreactive to NPY itself. After removal of the superior cervical ganglia bilaterally 22 days or 12 months before sacrifice, NPY-immunoreactive nerve fibers remained in the gland. This immunohistochemical study of the mink pineal gland therefore shows that the NPY/NPYamide-immunoreactive nerve fibers innervating the pineal gland in this species are a component of the central innervation or originate from extracerebral parasympathetic ganglia.

Animals↗

PubMed1982

Ultrastructure of the pineal gland of the fox.

The ultrastructure of the pineal gland of the fox was examined and compared with that of other mammals. The pineal gland of the fox is composed of two different populations of pinealocytes (I and II). The pinealocytes I were distributed homogeneously throughout the parenchyma, while pinealocytes II were located generally near blood vessels. A Golgi apparatus, granular endoplasmic reticulum, mitochondria, lysosomes, centrioles, and cilia were present in both cell populations. A characteristic feature of pinealocytes I was the presence of dense-core vesicles, presumably of Golgi origin; whereas glycogen deposits and pigment granules were common features of pinealocytes II. In addition to the pinealocytes, the parenchyma contained fibrous astrocytes. The capillaries of the pineal gland of the fox consisted of a nonfenestrated endothelium. Numerous never fibers, presumably adrenergic, were observed throughout the parenchyma.

Animals↗

PubMed1997

Regulation of glycogen content in rat pineal gland by norepinephrine.

In the rat pineal gland the glycogen stores were cytochemically localized in astrocytes and pinealocytes. Moreover, it was found that norepinephrine (NE) induced a time- and concentration-dependent reduction in pineal glycogen content and yielded lactic acid. The NE effect was prevented by blocking alpha1- but not alpha2 or beta-adrenoceptors. Activation of alpha2-adrenoceptors induced a small decrease in glycogen levels that could have pre- and postsynaptic components. Activation of beta-adrenoceptors with 10(-12)-10(-3) M isoproterenol (ISO) induced a bell shape concentration-response curve, presumably due to desensitization, since the response induced by 10(-4) M ISO was greater with shorter period of stimulation. On the other hand, activation of alpha1-adrenoceptors with 10(-12)-10(-3) M phenylephrine (PHN) induced a hyperbolic concentration-response curve with a maximum at concentrations above 10(-8) M. Moreover, treatment with ISO drastically reduced the response induced by PHN concentrations lower but not higher than 10(-6) M, favoring a concentration-dependent response between 10(-6) and 10(-4) M PHN, similar to that induced by equimolar NE concentrations. Thus, the NE-induced reduction in glycogen content of the rat pineal gland is mainly mediated by alpha1-adrenoceptors and modulated by intracellular mechanisms activated by beta-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1996

Development of the pineal gland: measurement with MR.

PURPOSE: To use MR imaging in the analysis of the size of the normal pineal gland in infants, children, and adolescents. METHODS: We retrospectively analyzed the size of the pineal gland in 249 patients (129 male and 120 female) aged 2 weeks to 20 years old. The maximum length (L), height (H), and width (W) of the gland were determined from a combination of sagittal, coronal, and axial MR images obtained on a 1.5-T scanner. The volume was calculated by using the formula 1/2 x L x H x W. RESULTS: The size of the pineal gland was significantly smaller in patients younger than 2 years old than in older patients. The size of the pineal gland increased until 2 years of age and remained stationary between the ages of 2 and 20 years. We found a large variation in size among all age groups. No difference in size was noted between males and females. CONCLUSION: This study establishes norms for pineal gland size in infants younger than 2 years old and in children and adolescents 2 to 20 years old as detected with MR imaging. Knowledge of the size of the normal pineal gland is important in the detection of abnormalities of the pineal gland, particularly neoplasms.

Adolescent↗

PubMed1984

No correlation of pineal "synaptic" ribbon numbers and melatonin formation in individual rat pineal glands.

As previous circadian studies of pineal "synaptic" ribbon numbers and melatonin formation suggested that a positive correlation of the two variables exists, in the present investigation this problem was examined in individual pineal glands of rats killed at 1200 h and 2400 h, respectively. For this purpose, one half of the gland was processed for electron microscopy and the ribbons were counted in an area of 20,000 micron2 tissue; in the other half serotonin N-acetyltransferase (NAT) activity and melatonin content were determined. No correlation was found to exist between ribbon numbers and pineal NAT activity, pineal melatonin levels and serum melatonin levels, either at day- or at nighttime. It is concluded that the ribbons may perhaps be more closely related to the innervation of the pineal gland than to melatonin formation.

Animals↗

PubMedDate not supplied

Trigeminal innervation of the mammalian pineal gland.

There is evidence that the trigeminal (Gasserian) ganglia innervate the mammalian pineal gland and serve in its regulation in addition to the sympathetic and cholinergic as well as further influences. By means of immunohistochemical methods, previous studies demonstrated fibers containing calcitonin gene-related peptide (CGRP-LI) or substance P (SP) in the superficial pineal of various mammalian species. In addition, SP and the related tachykinin, neurokinin A, were detected by radioimmunoassay and HPLC, respectively, in the rat and human pineal gland. In the present study, retrograde neuronal tracing upon injection of a tracer substance into the superficial pineal gland of rats was used in combination with immunohistochemistry to show that trigeminal ganglionic neurons innervate the gland, and that a considerable amount of these neurons are also CGRP- or SP-immunoreactive. These results reveal that afferent neuropeptidergic entering the superficial pineal gland originate from the trigeminal ganglia. The present paper reviews the evidence for a CGRP- and SP-ergic innervation of the mammalian pineal gland and discusses the possible role of these neuropeptides with regard to pineal function.

Animals↗

PubMed1998

Pharmacological, molecular and functional characterization of vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptors in the rat pineal gland.

Melatonin secretion from the mammalian pineal gland is strongly stimulated by noradrenaline and also by vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Three types of receptors for VIP and PACAP have been characterized so far: VIP1/PACAP receptors and VIP2/PACAP receptors, which possess similar high affinities for VIP and PACAP, and PACAP1 receptors which exhibit a 100-1000-fold higher affinity for PACAP. The aim of the present study was to characterize the receptor subtype(s) mediating the stimulatory effects of VIP and PACAP on melatonin synthesis in the rat pineal gland. Autoradiographic studies showed that PACAP and VIP were equally potent in displacing binding of radioiodinated PACAP27 from pineal sections. Amplification of pineal complementary DNAs by polymerase chain reaction using specific primers for the different receptor subtypes revealed that all three receptor messenger RNAs are expressed and that VIP1/PACAP receptor messenger RNA was predominant over VIP2/PACAP receptor messenger RNA. In vitro, VIP and PACAP stimulated melatonin synthesis with similar high potency and the effect of the two peptides were not additive. The selective VIP1/PACAP receptor agonists [R16]chicken secretin (1-25) and [K15, R16, L27]VIP(1-7)/growth hormone releasing factor(8-27) were significantly more potent than the selective VIP2/PACAP receptor agonist RO 25-1553 in stimulating melatonin secretion. The stimulatory effects of VIP and PACAP were similarly inhibited by the VIP1/PACAP antagonist [acetyl-His1, D-Phe2, K15, R16, L27]VIP(3-7)/growth hormone releasing factor(8-27). These data strongly suggest that VIP and PACAP exert a stimulatory effect on melatonin synthesis mainly through activation of a pineal VIP1/PACAP receptor subtype.

Adenylyl Cyclases↗

PubMed2001

The originality of Descartes' theory about the pineal gland.

René Descartes thought that the pineal gland is the part of the body with which the soul is most immediately associated. Several prominent historians (such as Soury, Thorndike and Sherrington) have claimed that this idea was not very original. We re-examine the evidence and conclude that their assessment was wrong. We pay special attention to the thesis about the pineal gland which Jean Cousin defended in January, 1641.

History, 17th Century↗

PubMed1993

An immunohistochemical study of neuropeptide Y in the bovine pineal gland.

An immunohistochemical study of the bovine pineal gland was performed using rabbit polyclonal antibodies raised against neuropeptide Y (NPY) or against the C-terminal flanking peptide of proNPY (CPON). A large number of NPY/CPON-immunoreactive (IR) nerve fibers were demonstrated throughout bovine pineal gland. The IR-fibers were located in the capsule of the gland, usually piercing into the gland together with blood vessels. In the gland itself, the fibers were also located intraparenchymally between the pinealocytes. Within the rostral and caudal areas of the pineal stalk, NPY-IR fibers were also observed, and these fibers could be followed not only into the gland but also to the habenular and posterior commissures. The morphological localization of the NPY-IR nerve fibers in the bovine pineal gland indicate that the majority of fibers originate from the superior cervical ganglion. However, some fibers probably originate from the brain itself.

Animals↗

PubMedDate not supplied

Pertussis toxin-sensitive G protein modulates the ability of histamine to stimulate cAMP production in the chick pineal gland.

Histamine (HA) is a potent stimulator of cAMP synthesis in various structures of chick brain, including the pineal gland. The action of HA is mediated by specific, membrane bound H(2)-like receptors, whose pharmacological profile is different from that described for H(2) receptors in mammalian tissues. In this work, we analyzed the effects of cholera toxin (CTX) and pertussis toxin (PTX), well-known modulators of G(s) and G(i)/G(o) protein, respectively, on the stimulatory action of HA on cAMP synthesis in the chick pineal gland organ cultures. HA and its two biologically active methylated derivatives, 2-methylHA and 4-methylHA, markedly increased cAMP content in the chick pineal glands. Pretreatment of the chick pineal glands with CTX potently stimulated basal cAMP production. In CTX-pretreated glands, elevations of cAMP synthesis evoked by HA, 2-methylHA and 4-methylHA were additive to those produced by CTX, which is an observation suggesting that H(2)-like HA receptors in the chicken pineal gland are not coupled to G(s) proteins. Pretreatment of the chick pineal glands with PTX significantly enhanced the stimulatory effect of HA and, to a greater extent, 2-methylHA on cAMP production. The enhancing action of PTX on the HA-evoked cAMP formation was not modified by mepyramine, a selective H(1)-type HA receptor antagonist. It is suggested that in the chick pineal gland, a population of HA receptors is coupled to G(i) (or G(o)) protein. Stimulation of these receptors would tonically suppress the activity of the cAMP generating system functionally linked to H(2)-like HA receptors.

Animals↗