Spontaneous pinealoma in a male Crj:CD (SD) IGS rat.
A pinealoma (benign) was found in a 61-week-old male Crj:CD (SD) IGS rat. The neoplasm was located between the cerebral hemispheres and the cerebellum. Histologically, the tumor cells consisted of two cell types: large, pale-staining cells and small dark-staining cells. A fibrovascular stroma divided the tumor cells into incomplete lobules or nest structures. Relatively numerous mitoses were noted in the tumor cells. Ultrastructurally, the tumor cells contained dense-cored vesicles, approximately 120 nm in diameter. (+info)
Pharmacological characterization of beta2-adrenoceptor in PGT-beta mouse pineal gland tumour cells.
1. The adrenoceptor in a mouse pineal gland tumour cell line (PGT-beta) was identified and characterized using pharmacological and physiological approaches. 2. Adrenaline and noradrenaline, adrenoceptor agonists, stimulated cyclic AMP generation in a concentration-dependent manner, but had no effect on inositol 1,4,5-trisphosphate production. Adrenaline was a more potent activator of cyclic AMP generation than noradrenaline, with half maximal-effective concentrations (EC50) seen at 175+/-22 nM and 18+/-2 microM for adrenaline and noradrenaline, respectively. 3. The addition of forskolin synergistically stimulated the adrenaline-mediated cyclic AMP generation in a concentration-dependent manner. 4. The pA2 value for the specific beta2-adrenoceptor antagonist ICI-118,551 (8.7+/-0.4) as an antagonist of the adrenaline-stimulated cyclic AMP generation were 3 units higher than the value for the betaI-adrenoceptor antagonist atenolol (5.6+/-0.3). 5. Treatment of the cells with adrenaline and forskolin evoked a 3 fold increase in the activity of serotonin N-acetyltransferase with the peak occurring 6 h after stimulation. 6. These results suggest the presence of beta2-adrenoceptors in mouse pineal cells and a functional relationship between the adenylyl cyclase system and the regulation of N-acetyltransferase expression. (+info)
Two arylalkylamine N-acetyltransferase genes mediate melatonin synthesis in fish.
Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT, EC 184.108.40.206) is the first enzyme in the conversion of serotonin to melatonin. Large changes in AANAT activity play an important role in the daily rhythms in melatonin production. Although a single AANAT gene has been found in mammals and the chicken, we have now identified two AANAT genes in fish. These genes are designated AANAT-1 and AANAT-2; all known AANATs belong to the AANAT-1 subfamily. Pike AANAT-1 is nearly exclusively expressed in the retina and AANAT-2 in the pineal gland. The abundance of each mRNA changes on a circadian basis, with retinal AANAT-1 mRNA peaking in late afternoon and pineal AANAT-2 mRNA peaking 6 h later. The pike AANAT-1 and AANAT-2 enzymes (66% identical amino acids) exhibit marked differences in their affinity for serotonin, relative affinity for indoleethylamines versus phenylethylamines and temperature-activity relationships. Two AANAT genes also exist in another fish, the trout. The evolution of two AANATs may represent a strategy to optimally meet tissue-related requirements for synthesis of melatonin: pineal melatonin serves an endocrine role and retinal melatonin plays a paracrine role. (+info)
No effect of pinealectomy on the parallel shift in circadain rhythms of adrenocortical activity and food intake in blinded rats.
Twenty-four-hr patterns of plasma corticosterone levels were determined at 4-hr intervals every 3-4 weeks in sighted and blinded pinealectomized rats of adult age. Through the whole period of the experiment, 24-hr patterns of food intake were also measured weekly. The sighted rats manifested the same 24-hr patterns of plasma corticosterone levels and food intake for 15 weeks after pinealectomy as those observed in the intact control rats. The magnitude of peak levels of plasma corticosterone and the amount of food intake did not differ between the two groups. A phase shift in circadian rhythms of plasma corticosterone levels and food intake was observed in both groups of blinded rats, with and without pinealectomy. Between the two groups, the patterns of phase shift were essentially similar for 10 weeks examined after optic enucleation. The peak elevation of plasma levels took place at 11 p.m. at the end of the 4th week after optic enucleation. Thereafter, 4- to 8-hr delay of peak appearance was observed every 3 weeks. No significant differences were found in peak values between the two groups of blinded rats. Furthermore, the circadian rhythm of food intake shifted in parallel with that of plasma corticosterone levels. A phase reversal of these two activities was observed between the 8th and 10th week after the operation. These results indicate that the pineal gland does not play any important role either in the maintenance of normal circadian periodicities of adrenocortical activity and food intake or in the shift in circadian rhythms of the two activities in the blinded rats. (+info)
Interstrain differences in activity pattern, pineal function, and SCN melatonin receptor density of rats.
We investigated the possibility that strain-dependent differences in the diurnal pattern of wheel running activity rhythms are also reflected in the melatonin profiles. The inbred rat strains ACI/Ztm, BH/Ztm, and LEW/Ztm. LEW were examined for diurnal [12:12-h light-dark (LD)] wheel running activity, urinary 6-sulphatoxymelatonin (aMT6s) excretion, melatonin concentrations of plasma and pineal glands, and melatonin receptor density in the suprachiasmatic nuclei (SCN). ACI rats displayed unimodal activity patterns with a high level of activity, whereas BH and LEW rats showed multimodal activity patterns with ultradian components and reduced activity levels. In contrast, the individual daily profiles of aMT6s excretion and mean melatonin synthesis followed a unimodal time pattern in all three strains, suggesting that different output pathways of the SCN are responsible for the temporal organization of locomotor activity and pineal melatonin synthesis. In addition, melatonin synthesis at night and SCN melatonin receptor density at day were significantly higher in BH and LEW rats than in ACI rats. These results support the hypothesis of a long-term stimulating effect of melatonin on its own receptor density in the SCN. (+info)
Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors.
In mammals, ocular photoreceptors mediate an acute inhibition of pineal melatonin by light. The effect of rod and cone loss on this response was assessed by combining the rd mutation with a transgenic ablation of cones (cl) to produce mice lacking both photoreceptor classes. Despite the loss of all known retinal photoreceptors, rd/rd cl mice showed normal suppression of pineal melatonin in response to monochromatic light of wavelength 509 nanometers. These data indicate that mammals have additional ocular photoreceptors that they use in the regulation of temporal physiology. (+info)
Transcription factors in neuroendocrine regulation: rhythmic changes in pCREB and ICER levels frame melatonin synthesis.
Neurotransmitter-driven activation of transcription factors is important for control of neuronal and neuroendocrine functions. We show with an in vivo approach that the norepinephrine cAMP-dependent rhythmic hormone production in rat pineal gland is accompanied by a temporally regulated switch in the ratio of a transcriptional activator, phosphorylated cAMP-responsive element-binding protein (pCREB), and a transcriptional inhibitor, inducible cAMP early repressor (ICER). pCREB accumulates endogenously at the beginning of the dark period and declines during the second half of the night. Concomitant with this decline, the amount of ICER rises. The changing ratio between pCREB and ICER shapes the in vivo dynamics in mRNA and, thus, protein levels of arylalkylamine-N-acetyltransferase, the rate-limiting enzyme of melatonin synthesis. Consequently, a silenced ICER expression in pinealocytes leads to a disinhibited arylalkylamine-N-acetyltransferase transcription and a primarily enhanced melatonin synthesis. (+info)
Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia.
Large infarcts develop in pinealectomized rats subjected to middle cerebral artery occlusion, which was attributed to loss of antioxidant action of melatonin. However, melatonin also has vascular actions, and pinealectomy may induce hypertension. The authors investigated (1) whether hemodynamic factors contribute to infarct development in pinealectomized rats, (2) whether melatonin administration can reverse the unfavorable effect of pinealectomy on infarct formation, and (3) whether melatonin can reduce the infarct volume in nonpinealectomized rats subjected to focal transient ischemia (2 hours middle cerebral artery occlusion, 22 hours reperfusion). Rats were pinealectomized 3 months before ischemia to eliminate any possible action of pinealectomy-induced hypertension on stroke. Blood pressure and regional CBF values during ischemia and reperfusion were not significantly different between pinealectomized and sham-operated rats, suggesting that pinealectomy-induced increase in infarct was not related to hemodynamic factors. The infarct volume resumed to the level of sham-operated rats on melatonin administration. Injection of melatonin (4 mg/kg) before both ischemia and reperfusion reduced infarct volume by 40% and significantly improved neurologic deficit scores in pinealectomized as well as sham-operated rats subjected to middle cerebral artery occlusion. These data suggest that physiologic melatonin release as well as exogenously given melatonin has a neuroprotective action in focal cerebral ischemia. (+info)