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PubMed2004

Day-night changes in downstream regulatory element antagonist modulator/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland.

The molecular mechanisms controlling the oscillatory synthesis of melatonin in rat pineal gland involve the rhythmic expression of several genes including arylalkylamine N-acetyltransferase (AA-NAT), inducible cAMP early repressor (ICER), and Fos-related antigen-2 (fra-2). Here we show that the calcium sensors downstream regulatory element antagonist modulator/potassium channel interacting protein (DREAM/KChIP)-3 and KChIP-1, -2 and -4 bind to downstream regulatory element (DRE) sites located in the regulatory regions of these genes and repress basal and induced transcription from ICER, fra-2 or AA-NAT promoters. Importantly, we demonstrate that the endogenous binding activity to DRE sites shows day-night oscillations in rat pineal gland and retina but not in the cerebellum. The peak of DRE binding activity occurs during the day period of the circadian cycle, coinciding with the lowest levels of fra-2, ICER, and AA-NAT transcripts. We show that a rapid clearance of DRE binding activity during the entry in the night period is related to changes at the posttranscriptional level of DREAM/KChIP. The circadian pattern of DREAM/KChIP activity is maintained under constant darkness, indicating that an endogenous clock controls DREAM/KChIP function. Our data suggest involvement of the family of DREAM repressors in the regulation of rhythmically expressed genes engaged in circadian rhythms.

Animals↗

PubMedDate not supplied

[Role of the pineal gland in the body protection from injury].

Pineal gland phylogenic antiquity, its involvement in the stress reaction and many-sided activity of its compounds permit to consider the gland to be the organ taking an active part in the body protection against injury, which is essential for everyone since its appearance on the planet. The available data prove that almost all the reactions developing in the organism from the moment of trauma up to the complete wound reparation are under the pineal control. Being always an urgent one the problem of traumatism increased nowadays because of pineal dysfunction. It makes the premises to apply pineal secret products in traumatic disease as a kind of replace therapy that is suggested to be not less successful than glucocorticoid administration in shock.

Animals↗

PubMed2001

Hypocretin (orexin) in the rat pineal gland: a central transmitter with effects on noradrenaline-induced release of melatonin.

Hypocretin-1 (HCRT-1) and hypocretin 2 (HCRT-2), also known as orexin-A and orexin-B, are two neuropeptides derived from the same precursor. Hypocretinergic neurons have been found exclusively in the hypothalamic dorsolateral area. These neurons are implicated in sleep and feeding through activation of specific G-protein-coupled orexin-1 and orexin-2 receptor (OR-R1 and OR-R2). The purpose of this study was to determine the existence of the HCRT peptides in the central input of the rat pineal gland. Further, OR-R1 and OR-R2 expression was determined in the pineal gland and the effect of HCRT-2 on melatonin synthesis and secretion was analysed in dissociated rat pinealocytes. A large contingent of HCRT-positive nerve fibres and terminals were observed in the epithalamus, many of which entered into the pineal parenchyma. A significant number of nerve fibres endowed with positive boutons were identified in the pineal stalk, though the number of positive fibres decreased along the extension of the stalk. So far, no positive fibres have been found in the superficial pineal gland. RT-PCR analysis revealed the expression of OR-R2 mRNA, whereas OR-R1-receptor mRNA was not detected. When tested alone, HCRT-2 had no effect on secretion of melatonin from cultured rat pinealocytes. However, HCRT-2 partially inhibited (by a maximum of 30%) the beta-adrenergic-induced melatonin secretion. The same effect was seen on activation of N-acetyltransferase activity. The distribution and the large number of HCRT-positive fibres together with the effect on noradrenaline-mediated melatonin release through specific receptors suggests that these peptides may be significant central transmitters in pineal function, probably mediating homeostatic signals to the pineal gland.

Acetyltransferases↗

PubMed1989

Studies on the properties of muscarinic cholinergic receptor sites in bovine pineal gland.

1. Using the tritiated muscarinic receptor antagonist, quinuclidinyl benzilate ([3H]QNB) as a ligand, muscarinic cholinergic receptors have been identified and characterized in the pineal glands of cow and swamp buffalo. 2. At 25 degrees C, the specific binding reached equilibrium within 60 min and remained constant for an additional two hours. Furthermore, the specific binding was saturable, reversible and tissue dependent in nature. 3. The kinetic analyses of muscarinic cholinergic receptor sites revealed KD values of 0.423 +/- 0.01 nM and 0.218 +/- 0.01 nM, and Bmax values of 69.75 +/- 20.91 fmol/mg protein and 74.19 +/- 32.73 fmol/mg protein for the cow's- and the swamp buffalo's pineal glands, respectively. 4. The presence of muscarinic cholinergic receptor sites originating from cholinergic innervation of the pineal gland is suggested.

Animals↗

PubMed1994

Presence of P2-purinoceptors in the rat pineal gland.

1. The effects of noradrenaline, ATP, adenylyl-imidodiphosphate (AMP-PNP), adenosine, alpha,beta-methylene-ATP and the P2-purinoceptor antagonist, suramin on N'-acetyl-5-hydroxytryptamine production were studied in cultured denervated rat pineal glands. 2. Noradrenaline (3 nM-1 microM) increased N'-acetyl-5-hydroxytryptamine production as measured both in the gland and the culture medium. 3. In noradrenaline (10 nM)-stimulated pineal glands, ATP (0.03 nM-1 mM) or AMP-PNP (0.1 microM-1 mM) increased N'-acetyl-5-hydroxytryptamine production in a concentration-dependent manner. 4. Alpha,beta-Methylene-ATP at the concentration of 0.1 mM, but not 3 microM, attenuated the enhancement by ATP (0.1 mM) of noradrenaline (10 nM)-induced N'-acetyl-5-hydroxytryptamine production. 5. Suramin (0.1 mM) blocked the potentiating effect of ATP (0.1 mM), but not the potentiating effect of adenosine (0.1 mM) in glands incubated with noradrenaline (10 nM). 6. These findings suggest that the rat pineal gland possesses P2-purinoceptors which when stimulated potentiate the effect of noradrenaline but do not, by themselves, induce an increase in N'-acetyl-5-hydroxytryptamine production.

Adenosine↗

PubMed1977

Hydroxyindole-O-methyl transferase (HIOMT) and serotonin in the pineal gland of the vizcacha (Lagostomus maximus maximus).

Pineal glands of vizcachas collected from their natural habitat were studied. Hydroxyindole-O-methyl transferase (HIOMT) activity showed a great individual dispersion. However, the enzyme activity was significantly higher in males than in females. Serotonin was also assayed in the glands. It did not show significant differences between both sexes. The results are discussed in relation to the natural life conditions of this rodent.

Acetylserotonin O-Methyltransferase↗

PubMed1988

Cytodifferentiation of the chick pineal gland, with special reference to the photosensory and secretory elements.

Cytodifferentiation of the chick pineal gland throughout the embryonic development was investigated with light and electron microscopy. The chick pineal anlage appears first as a small evagination in the diencephalic roof at 60 h of incubation (27-30 somites). Until day 5 of incubation, pineal anlage cells are undifferentiated and appear similar to ventricular ependymal cells. Subsequently, pinealocytes and supporting cells are first distinguishable at 7-8 days, and parafollicular cells are distinguishable at 12 days of incubation. Pigment-containing cells after 6 days and nerve cells after 17 days of incubation gradually increase, especially in the posterior wall of the pineal recess. During embryonic development, the chick pineal gland has both photosensory and secretory elements: viz. the former, mitochondria-laden apical protrusions, synaptic ribbons, lamellar whorl-like cilia of the pinealocytes, and adjacent appearance of the pigment-containing cells and the nerve cells; and the latter, dense-cored vesicles of the pinealocytes and dense bodies of the supporting cells. Moreover, nuclear invaginations having a large lipid droplet nearby and some aggregations of glycogen are found in the pinealocytes and are transitory changes in structure restricted to certain days of incubation.

Animals↗

PubMed2001

A reproductive phase-dependent effect of dietary L-tryptophan on pineal gland and gonad of a nocturnal bird, Indian spotted owlet Athene brama.

Unlike other temperate owls, Indian spotted owlet Athene brama possesses a well-developed pineal gland that secrets moderate amount of hydroxy- (serotonin) and methoxy- (melatonin) indoles in circulation. However, in this study, we have reported the response of this endocrine gland to exogenous L-Tryptophan (precursor of the above indoles), and also its effect on gonads of this nocturnal bird. During breeding phase or pineal inactive phase (March), oral treatment of L-Trp (0.5 mg/100 g Bwt/day) significantly increased the pineal gland wt and plasma melatonin (MEL) level, while decreased the gonadal wt and plasma sex steroids levels (estradiol and progesterone in female and testosterone in male). Interestingly, during reproductively quiescent phase or pineal active phase (August), similar amount of L-Trp significantly decreased the plasma MEL level, while increased the above sex steroid levels in plasma. Finally, the results show a clear reproductive phase-dependent inverse effect of L-Trp on pineal gland and gonads for both sexes of the spotted owlets, and suggest that the therapeutic use of this amino acid would be a great advantage for controlling the reproduction of these economically important birds.

Animals↗

PubMed1990

[Light microscopic observations on intrapineal neurons and myelinated fibers distributed in the pineal gland and its capsule in cotton rats (Sigmodon hispidus) at various postnatal ages].

From birth to 300 days, neurons are mainly encountered in the distal third of the pineal gland. Neurons are scarce in the middle or proximal third; their number is fewer in the proximal third. Nuclear size of neurons in all pineal regions increases until 100-200 day. Since there are regional differences in size of nuclei of intrapineal neurons in cotton rats until 200 days, intrapineal neurons of this animal may be composed of different populations of cells. The observation that age changes in size of nuclei of intrapineal neurons are similar to those of pinealocytes suggests that such neuronal changes may be related to the functional differentiation of the organ. In all pineal regions, the number of neurons reduces to half from birth to 100 days. The enlargement of neuronal nuclei and the decrease in neuronal numbers proceed simultaneously with advancing age. Half the number of neurons may degenerate and disappear until 100 days. Myelinated fibers in the pineal gland and its capsule appear first at 20 days and their density increases with age. Myelinated fibers are mainly distributed in the distal pineal region and the capsule covering its posteroventral area. Since neurons are mainly located in the posteroventral area of the distal pineal region, a close topographical relation exists between myelinated fibers and intrapineal neurons. The myelinated fibers in the capsule may usually run from distal to proximal regions of the pineal gland; some of these fibers may enter the organ.

Aging↗

PubMed1986

Electrophysiological and endocrinological aspects of aging in the rat pineal gland.

Previous morphological and biochemical studies point to an age-dependent loss of pineal gland function. In order to investigate the possible alterations of electrical activity of aged rat pineal glands, electrophysiological recordings in 3- and 18-month-old male Sprague-Dawley rats were undertaken at both daytime and nighttime. Extracellularly recorded action potentials were characterized according to discharge frequency and serum melatonin levels were determined concomitantly. Significant differences in the frequency distributions between young adult and old rats were found to occur at nighttime, with a shift towards lower frequencies in old animals. Serum melatonin levels were reduced significantly in old rats and the characteristic nocturnal peak was attenuated. These results demonstrate a distinct decrease of pineal electrical and secretory activity with advancing age, which may contribute to an age-dependent decline of neuroendocrine capacity.

Action Potentials↗

PubMed1975

Fine structural changes in the hamster pineal gland after blinding and superior cervical ganglionectomy.

Pineal glands of male hamsters 8 weeks after removal of both eyes or both superior cervical ganglia and those of untreated animals were studied by electron microscopy. In the blinded hamsters the reproductive organs were remarkably involuted, whereas the pinealocytes enlarged and were characterized by a tremendous hypertrophy of the smooth-surfaced endoplasmic reticulum, in the mesh of which some dense cored vesicles were distributed. In constrast the pinealocytes of ganglionectomized hamsters atrophied and were noted by a large number of lysosomes and sparsity of the agranular reticulum, the testes being significantly larger than the controls. The findings were interpreted to be compatible with the view that the pineal capability of producing antigonadal substance is augmented by blinding and is suppressed by cervical ganglionectomy due to the impairment of normal functioning of the pineal by denervation. It is assumed that the degree of development of the smooth endoplasmic reticulum in the pinealocyte is parallel to, and reflects that of the pineal activity. Probably the membranous organelle is involved in the elaboration of the pineal antigonadal substance.

Animals↗

PubMed1976

[Comparison of the intraspecific growth of the endocranial organs (hypophyseal lobes, pineal gland, SFO) in the white Wistar rat. Rattus norvegicus (Berkenhout), with their interspecific growth in the rodents].

The intraspecific growth of various endocranian organs (hypophysis, pineal gland and SFO) in the Rat compared to a group of Rodents shows that their allometry coefficient/somatic weight is : close to isometry for the anterior and intermediate lobes of the hypophysis which is suitable for endocrine glands; lower and close to that found for the relation brain weight/somatic weight for the nervous lobe in the Rat and in Rodents; and extremely low (0,33) for the SFO in the Rat, which is comparable to that found in Rodents (0,44). The allometry coefficient found for the pineal gland is not comparable to that found in Rodents (1,25). Many facts (important intra and interspecific variations, existence of species or individuals deprived of pineal gland) seem to indicate that this gland is not related to an essential somatic function.

Animals↗

PubMed1993

A comparative study of melatonin production in the retina, pineal gland and harderian gland of Bufo viridis and Rana esculenta.

1. The circadian patterns of melatonin and of its synthesizing enzyme N-acetyltransferase (NAT) were investigated in the serum, retina, pineal gland and Harderian gland (HG) of two amphibian species, Bufo viridis and Rana esculenta. 2. Serum melatonin levels showed no diurnal fluctuations in Bufo viridis, whereas, in Rana esculenta, they exhibited a circadian rhythm, with the highest values occurring during the night. Retina melatonin exhibited characteristic circadian patterns in both species, with the highest values occurring during the day, in Bufo, and the highest concentrations occurring at night in Rana. 3. In the retina, NAT activity peaked at night in both amphibians, but in Bufo the levels were up to 30 times higher than in Rana. In the HG and in the pineal gland, NAT activity showed different patterns in the two species with no diurnal variations in Bufo, and characteristic circadian rhythms in Rana. 4. In the HG and pineal gland of both species, melatonin was only occasionally detectable over the 24-hr period. 5. This is the first report exploring melatonin production in Bufo viridis and Rana esculenta. In our experimental conditions, marked differences emerged between the two species.

Animals↗

PubMed1987

Multiple forms of arylalkylamine N-acetyltransferases in the rat pineal gland: purification of one molecular form.

Rat pineal serotonin N-acetyltransferase (EC 2.3.1.87) activity is isolated in two molecular forms (Mr approximately equal to 10,000 and 95,000) by high performance size exclusion liquid chromatography in the presence of ammonium acetate (0.1 M, pH 6.5). In the presence of sodium citrate (0.1 M, pH 6.5), however, it is eluted as a single peak of intermediate size (Mr approximately equal to 30,000). A highly enriched preparation of one of the molecular forms has been obtained by a two-step purification procedure involving disulfide-exchange and anion-exchange chromatography. The N-acetyltransferase in 250 pineal glands obtained from isoproterenol-treated rats can be purified about 80-fold in 1 day; recovery is about 3%. Polyacrylamide gel electrophoresis of the final preparation indicates that a single major band (Mr approximately equal to 11,000) is present; this appears to be serotonin N-acetyltransferase.

Acetyltransferases↗

PubMed1996

Role of the pineal gland and melatonin in the development of autoimmune diabetes in non-obese diabetic mice.

Earlier studies on the immunoregulatory role of the pineal gland and melatonin revealed that melatonin counteracts immunosuppression and thymus atrophy induced by stress or corticosteroid treatment. Moreover, melatonin protects mice injected with encephalitogenic viruses, synergizes with interleukin-2 (IL-2) in cancer immunotherapy and rescues hematopoiesis from cancer chemotherapy toxicity. In regard to the mechanism of action, melatonin seems to act directly on CD4+ lymphocytes which release opioid peptides with immunoenhancing properties along with other cytokines. Because of these findings, we investigated the role of the pineal gland and melatonin in autoimmune diabetes mellitus type I using, as an experimental model, female non-obese diabetic (NOD) mice. Mice were pinealectomized or treated chronically with melatonin (injected subcutaneously or administered via drinking water). This paper shows that neonatal pinealectomy accelerates the development of the disease in female NOD mice while exogenous melatonin protects the animals. This in spite of the fact that melatonin increased the production of insulin autoantibodies (IAA). We conclude that the pineal gland and melatonin influence the development of autoimmune diabetes although the mechanism of action that needs further investigation.

Animals↗

PubMed1993

Effect of sympathetic denervation of the pineal gland on maternal co-ordination of the circadian rhythm of alpha-amylase in parotid gland from young rats.

Twenty-five-day-old rats maintained in constant darkness since birth and born from mothers kept in the dark since the 14th day of pregnancy showed a circadian rhythm of alpha-amylase content in parotid glands, which may be explained by a mechanism of maternal co-ordination. Rats in the same conditions, except that their mothers had been submitted to bilateral excision of the superior cervical ganglia 30 days before mating, did not show diurnal variations of alpha-amylase activity in the parotid glands. When ganglionectomized mothers were treated with a daily dose of melatonin (1 mg/kg) from the 14th day of gestation up to the 10th day of lactation, their litters showed significant diurnal variations of amylase in the parotid glands, suggesting a role of the maternal pineal gland in the maternal-fetal and/or maternal-neonatal transfer of photoperiodic information.

Animals↗

PubMed1981

Prostaglandin E2 increases adenosine 3',5'-monophosphate concentration and binding-site occupancy, and stimulates serotonin-N-acetyltransferase activity in rat pineal glands in vitro.

The effects of prostaglandins (PGs) on rat pineal metabolism were examined in vitro. PGE2 (0.01-1 microM) increased the activity of serotonin-N-acetyltransferase (SNAT), the stimulation curve exhibiting a maximum at 0.1 microM. PGE1 increased SNAT activity only at the highest dose (1 microM) whereas PGF2 alpha, 15-keto-PGF2 alpha or PGI2 did not affect the enzymic activity. The stimulation of SNAT activity brought about by PGE2 in pineals from ganglionectomized rats was greater than in sham-operated controls at all the doses studied, suggesting that the observed effect is predominantly post-synaptic. Only PGE2 significantly increased pineal cAMP accumulation in vitro at doses between 0.01 and 1 microM, and depressed the unoccupied cAMP-binding sites in pineal 900 g supernatants. The total number of cAMP-binding sites remained unaltered after incubation of PGE2. The present observations together with the previously reported NE-induced release of PGs in incubated pineal glands, the occurrence of pineal PG-binding sites and the indomethacin blockade of the nocturnal rise of pineal SNAT and melatonin content, support a role for PGs in the control of melatonin synthesis.

Acetyltransferases↗

PubMed2005

Circadian gene expression patterns of melanopsin and pinopsin in the chick pineal gland.

The directly light-sensitive chick pineal gland contains at least two photopigments. Pinopsin seems to mediate the acute inhibitory effect of light on melatonin synthesis, whereas melanopsin may act by phase-shifting the intrapineal circadian clock. In the present study we have investigated, by means of quantitative RT-PCR, the daily rhythm of photopigment gene expression as monitored by mRNA levels. Under a 12-h light/12-h dark cycle, the mRNA levels of both pigments were 5-fold higher in the transitional phase from light to dark than at night, both in vivo and in vitro. Under constant darkness in vivo and in vitro, the peak of pinopsin mRNA levels was attenuated, whereas that of melanopsin was not. Thus, whereas the daily rhythm of pinopsin gene expression is dually regulated by light plus the intrapineal circadian oscillator, that of melanopsin appears to depend solely on the oscillator.

Adaptation, Ocular↗