Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate cis-elements responsible for catecholaminergic (CAnergic) neuron-specific expression of the tyrosine hydroxylase (TH) gene, we produced lines of transgenic mice carrying 5.0-kb, 2.5-kb and 0.2-kb fragments from the 5'-flanking region of the human TH gene fused to a reporter gene, chloramphenicol acetyltransferase (CAT), and designated them as TC 50, TC 25, and TC 02, respectively, and reporter gene expression in transgenic mice was analyzed by CAT assay by immunocytochemistry with anti-CAT antibody. High-level CAT expression was observed in the brain and adrenal gland using the 5.0-kb promoter of the TC 50 mice, but ectopic expression was consistently observed in several somatic tissues, e.g. thymus, colon, and testis. In brain, expression was achieved in CAnergic neurons with the largest construct (5.0 kb), but not with 2.5 kb or 0.2 kb of 5' flanking sequence. However, TC 50 mice also expressed CAT immunoreactivity in non-CAnergic neurons. In the TC 25 line CAT immunoreactivity was detected only in some non-CAnergic neurons. In the TC 02 line no CAT immunoreactivity was detected in any of the tissues examined. These results indicate that the 5.0-kb DNA fragment of the TH gene upstream region contains activity to express CAT in CAnergic neurons and surprisingly, lacks some regulatory elements attenuating ectopic expression, and that the 2.5-kb and 0.2-kb fragment are not sufficient for the proper expression. We discuss the presence of the tissue-specific regulatory elements in the structure portion of the TH gene and/or 3'-flanking region.
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PMID:Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice. 136 28

The peptidergic innervation of rat thymus has been investigated by immunohistochemical methods, focusing on the spatial interrelationship of peptidergic nerve fibers with mast cells and macrophages in the rat. An antiserum directed against the protein gene product 9.5 (PGP 9.5) regarded as a pan-neuronal marker revealed a rich innervation, especially in the subcapsular cortex, in interlobular septa, and of the vasculature in the cortex and the corticomedullary boundary. A minor proportion of PGP 9.5-immunoreactive (ir) fibers supplied the thymic parenchyma. The main component of peptidergic innervation consisted of fibers costaining for tachykinins (TKs) and calcitonin gene-related peptide (CGRP), but considerable amounts of neuropeptide Y (NPY)/tyrosine hydroxylase (TH)-positive fibers and vasoactive intestinal polypeptide/peptide histidine isoleucine-positive fibers also were present. There were sparse Leu-enkephalin and galanin immunoreactivities in thymic nerve fibers, while neurotensin was absent from nerve fibers. Close associations of TK/CGRP-ir and NPY-ir fibers with mast cells were frequently detected in the connective tissue areas of the thymus, often adjacent to the vasculature. TK/CGRP-ir fibers and some rare NPY-ir fibers were found adjacent to EDl-positive macrophages and less frequently to mast cells. TK/CGRP-ir and NPY-ir fibers were mainly detected in relation to the vasculature of the cortex and the corticomedullary boundary, but also were found in capsular and subcapsular regions of the thymic cortex. The possible importance of the close spatial relationship between the various peptide-containing nerve fibers and mast cells and ED1-positive macrophages in neuroimmune integration is discussed.
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PMID:Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus. 164 85

The identity of the neuronal nicotinic alpha-bungarotoxin (alpha-BGT) site, which appears to be distinct from the functional nicotinic receptor, is unclear. Recent work in our laboratory has shown that the thymus-derived polypeptide thymopoietin potently and specifically interacts at the nicotinic alpha-BGT site in brain. The present results show that thymopoietin also interferes with the binding of 125I-alpha-BGT to chromaffin cells in culture; a dose-dependent inhibition in binding was observed, with an IC50 of 10(-8) M. To assess the long term effect(s) of thymopoietin in nervous tissue, chromaffin cells were exposed to the polypeptide for varying periods of time. Incubation of the cells in culture with thymopoietin (10(-9) to 3 x 10(-7) M) for 2 to 7 days resulted in an approximate 3-fold increase in alpha-BGT binding. Saturation analysis indicated this was due to an increase in the Bmax. The thymopoietin-induced increase in binding could be reversed with nicotine: thus, the sites can be regulated by a nicotinic receptor ligand. Although thymopoietin potently interacted at the nicotinic alpha-BGT receptor, nicotinic receptor responsiveness was not affected after short or long term exposure to the peptide. Neither basal nor nicotinic receptor-stimulated tyrosine hydroxylase activity was altered by thymopoietin. As well, resting and acetylcholine-evoked noradrenaline release remained similar to control after exposure of the cells to the polypeptide. These results indicate that the thymic polypeptide thymopoietin specifically interacts with the nicotinic alpha-BGT receptor population and, furthermore, can regulate the toxin binding sites in chromaffin cells in culture.
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PMID:Thymopoietin, a thymic polypeptide, regulates nicotinic alpha-bungarotoxin sites in chromaffin cells in culture. 837 21

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.
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PMID:Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats. 396 Sep 94

Transgenic mice, expressing the gene for bovine growth hormone (bGH), exhibit increased body size, reduced reproductive capacity, and high basal levels of several hormones including corticosterone. Their shortened life span may be indicative of accelerated aging. As prominent astrogliosis of the CNS accompanies aging in rodents, bGH transgenic mice were examined for astrogliosis, as quantified by an ELISA for the astrocyte-localized protein, glial fibrillary acidic protein (GFAP). Transgenic mice were produced by mating C57BL/6 x C3H F1 hybrid females with male descendants of animals produced by microinjection of fertilized eggs with phosphoenolpyruvate carboxykinase (PEPCK)/bGH-hybrid gene. Transgenic mice (approximately 3.5 and approximately 12 months of age) weighed significantly more than same age or older (approximately 20 month) controls. Most of their internal organs, including the heart, kidneys, adrenals, liver, and spleen, were also heavier. In contrast, the thymus was heavier only in the younger transgenic mice. Serum corticosterone was highest in the older transgenic mice. A small but significant increase in whole brain, cortex, and cerebellar weight, relative to controls and the older transgenic mice, was found in the younger transgenic mice. Control mice exhibited large, significant age-related increases in GFAP. Increases of 35, 70, 68, 89, 79, and 95% for cortex, cerebellum, striatum, hippocampus, midbrain, and brain stem, respectively, were found when comparing the oldest (approximately 20 months) control mice to the youngest (approximately 3.5 months). In contrast, in the olfactory bulbs and the hypothalamus there were no age-related changes in the levels of GFAP in control mice. Transgenic mice (approximately 3.5 months) had significantly elevated GFAP levels relative to the same-age controls in all brain areas examined. In some brain areas, the GFAP levels found in the younger transgenic mice were equivalent to those found in the oldest controls. No differences between controls and transgenics were found in tyrosine hydroxylase protein levels of striatum or hypothalamus. The elevated GFAP levels of transgenic mice may reflect increased neural damage due to accelerated aging processes or damage associated with high circulating levels of bGH or corticosterone. Alternatively, the increased expression of GFAP in the transgenic mice may reflect altered regulation of GFAP rather than an increase signaled by neural damage.
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PMID:Increased glial fibrillary acidic protein (GFAP) levels in the brains of transgenic mice expressing the bovine growth hormone (bGH) gene. 755 16

The presence of peptidergic and noradrenergic sympathetic nerve fibers in specific compartments of both primary and secondary lymphoid organs of the rodent is well established. These nerve fibers directly contact lymphocytes and macrophages, as well as vascular and trabecular smooth muscle. We investigated the noradrenergic and neuropeptide-Y innervation of lymphoid organs in the cetacean, Delphinapterus leucas (beluga whale). The spleen, thymus, tonsil, gut-associated lymphoid tissue, and assorted lymph nodes were collected from five belugas, obtained during sanctioned hunts, and processed for catecholamine fluorescence histochemistry and for tyrosine hydroxylase and neuropeptide-Y immunocytochemistry. Innervation studies revealed fluorescent nerve fibers, tyrosine hydroxylase, and neuropeptide-Y positive nerve fibers in parenchymal lymphoid compartments, where they were closely associated with cells of the immune system, and in vascular and trabecular compartments. In lymphoid zones, tyrosine hydroxylase and neuropeptide-Y positive nerve fibers were observed in the periarteriolar lymphatic sheath and marginal zone of the spleen; in the outermost portion of the cortex, the corticomedullary zone, and medulla of the lymph nodes; in the parafollicular zones, and diffuse lymphocyte layer below the epithelium of the tonsil; in the outermost portion of some thymic lobules; and in the lamina propria of the gut. These findings are similar to those described for other mammals and substantiate an anatomical link between the nervous and immune systems in the beluga, whereby central nervous system activity may influence autonomic outflow to lymphoid organs and effect immunologic reactivity.
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PMID:Noradrenergic and peptidergic innervation of lymphoid organs in the beluga, Delphinapterus leucas: an anatomical link between the nervous and immune systems. 793 71

An immunohistochemical study was done for the presence of tyrosine hydroxylase (noradrenergic innervation), neuron-specific protein PGP9.5, and anterior pituitary hormones (beta-subunit of follicle-stimulating hormone, growth hormone, beta-subunit of luteinizing hormone, prolactin, and beta-subunit of thyroid-stimulating hormone) in cultured thymic fragments before and after transplantation in congenitally athymic and euthymic rats. The cultured thymic fragments consisted of epithelial cells and were depleted of lymphocytes. After implantation in syngeneic and allogeneic athymic recipients and in syngeneic euthymic recipients, a recovery of the original architecture was found within 6 weeks; rejection occurred within 3 weeks for allogeneic transplantation in euthymic rats. During culture nerve-like profiles almost disappeared from the tissue, and reappeared simultaneously with the influx of host-derived cells and the restoration of the original thymic architecture. A high immunoreactivity for hormones and PGP9.5 was found in epithelial cells after culture and in the first phase after transplantation. These epithelial cells may represent precursor-epithelial cells, based on their unusual ultrastructure and combined expression of markers that in the normal thymus occur only on subcapsular/medullary epithelium or on cortex epithelium. These data indicate a potential role of the neuroendocrine function of the thymus during restoration of the thymus architecture starting from precursor-like epithelial cells.
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PMID:The neuro-endocrine component of the rat thymus: studies on cultured thymic fragments before and after transplantation in congenitally athymic and euthymic rats. 809 23

The object of these experiments was to investigate whether noradrenaline is the signal neurotransmitter between the sympathetic nervous system and rat thymocytes. Using immunocytochemistry, evidence was obtained that the rat thymus (thymic capsule, subcapsular region and connective tissue septa) is innervated by noradrenergic varicose axons terminals (tyrosine hydroxylase- and dopamine-beta-hydroxylase-immunostained nerve fibres). This innervation is mainly associated with the vasculature and separately from vessels along the thymic tissue septa it branches into the thymic parenchyma. Using electron microscopy, classical synapses between thymocytes and neuronal elements were not observed. The neurochemical study revealed that these nerve terminals are able to take up, store and release noradrenaline upon axonal stimulation in a [Ca2+]o-dependent manner. The release was tetrodotoxin (1 microM)-sensitive, and reserpine pretreatment prevented axonal stimulation to release noradrenaline, indicating vesicular origin of noradrenaline. In addition, it was found that the release of noradrenaline was subjected to negative feedback modulation via presynaptic alpha 2-adrenoreceptors. Using a patch-clamp technique, electrophysiological evidence was obtained showing that noradrenaline inhibits in a concentration-dependent manner outward voltage-dependent potassium (k+) current recorded from isolated thymocytes. Since noradrenergic varicose axon terminals enter the parenchyma thymocytes and the boutons are not in close apposition to their target cells, noradrenaline released from these terminals diffuses away from release site to reach its targets, thymocytes, and to exert its inhibitory effect on voltage-dependent K+ -current. Since K+ channels are believed to be involved in T cell proliferation and differentiation, the modulation of K+ channel gating by noradrenaline released in response to axonal activity suggests that signals from blood-born or locally released hormones and cytokines. In this respect, noradrenaline released from non-synaptic neuronal varicosities and exerting its effect within the radius of diffusion may serve as a chemical link between the sympathetic nervous system and thymocytes and may have physiological and pathological importance in the thymus during stress and inflammatory/immune responses.
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PMID:Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes. 854 99

Two pharmacogenetically selected Wistar rat lines have been used as a model for individual variability in behavioral and neuroendocrine responses. As a selection criterion the behavioral responsiveness for the dopamine agonist apomorphine was used, giving rise to the apomorphine-susceptible (apo-sus) and apomorphine-unsusceptible (apo-unsus) rat lines. This selection has been maintained over 16 generations. Recent studies have shown that adult rats of these selection lines also show pronounced differences in responsiveness of the hypothalamic-pituitary-adrenal (HPA) system. In this study we analyzed to what extent the divergence in dopamine phenotype and HPA responsiveness, as observed in adult rats, are linked to possible differences, within both systems, during early postnatal development. Therefore, we measured in neonatal female rats of 10 and 18 days of age several parameters of the dopamine and HPA system which show significant differences in adult rats. These include tyrosine hydroxylase (TH) and dopamine D1 and D2 receptor mRNA levels, which were determined within the nigrostriatal system since this system shows the most pronounced differences between adult rats of both selection lines. As indices of HPA activity we measured CRH mRNA, ACTH and total and free corticosterone plasma concentrations under basal conditions in the morning. Transcripts of the two types of corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) receptor were measured in hippocampus and paraventricular nucleus. In 10-day-old rats all dopamine and HPA parameters were similar in rats of the two selection lines, except for GR mRNA in the parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN) of apo-sus rats, which was significantly higher than in apo-unsus rats. Eighteen-day-old apo-sus rats, however, showed significantly higher ACTH, comparable total corticosterone and a trend towards lower free corticosterone plasma levels. This HPA profile resembles the situation in adult apo-sus rats as compared with adult apo-unsus rats. Hippocampal GR mRNA expression and thymus weight were also higher in apo-sus rats. In addition, these rats showed an age-related increase in hippocampal MR mRNA expression, while in apo-unsus rats MR mRNA levels did not change between pnd 10 and 18. The measures of the nigrostriatal dopamine system at day 18 were still similar in rats of both lines. In conclusion, divergence in the dopamine systems of the two pharmacogenetically selected rat lines emerges subsequent to divergence in pituitary-adrenal activity.
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PMID:Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity. 873 23

Maternal deprivation of neonatal rats for 24 h enhances the adrenocortical response to stress and/or adrenocorticotropin hormone (ACTH) stimulation during the stress hyporesponsive period (SHRP). The present study tests the hypothesis that such maternally deprived neonatal male rats show altered hypothalamic-pituitary-adrenal (HPA) regulation not only immediately after deprivation but also in later life. In addition, we found previously that neonatal changes in HPA activity preceded modulation of nigrostriatal dopamine function. Therefore, we also measured dopamine responsiveness in adult rats which were deprived of their mother during infancy. Neonatal male rats were maternally deprived for 24 h at the age of 3 days, whereas rats of the control group were left undisturbed. At 60 days of age deprived and non-deprived rats were decapitated and brain, adrenal glands and thymus were removed. Trunk blood was collected for determination of plasma ACTH, corticosterone and prolactin concentrations using radioimmunoassay procedures. mRNA levels of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), corticotropin-releasing hormone (CRH) mRNA and tyrosine hydroxylase (TH) mRNA were measured in brain sections with in situ hybridization. In a second group of male deprived and non-deprived rats apomorphine-induced stereotypic gnawing behaviour was examined at 60 days of age as a measure for functional activity of the dopamine system. Deprived neonatal rats showed the following characteristics as compared with non-deprived rats: (i) lower basal CRH mRNA concentration in parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN), while basal plasma ACTH and corticosterone concentrations were significantly elevated. Basal prolactin levels were not different. (ii) Similar hippocampal MR and GR mRNA levels. (iii) Significantly reduced GR mRNA levels in PVN and anterior pituitary. (iv) Significantly enhanced apomorphine-induced stereotypic gnawing behaviour and (v) higher TH mRNA levels in substantia nigra, while no changes were found in the ventral tegmental area (VTA). It is concluded that maternally deprived neonatal male rats display as young adults elevated basal pituitary-adrenal activity and enhanced apomorphine susceptibility.
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PMID:Neonatal maternally deprived rats have as adults elevated basal pituitary-adrenal activity and enhanced susceptibility to apomorphine. 884 18


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