Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.14.16.2 (tyrosine hydroxylase)
14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mouse, rat, and monkey, N-methyl-D,L-aspartic acid (NMDA) modulates gonadotropin releasing hormone (GnRH) release by an unknown mechanism. In previous studies we found that normal male mice consistently responded to NMDA administration with increased levels of plasma LH, as did most normal female mice and female hypogonadal mice with fetal preoptic area implants (HPG/POA). To investigate the mechanism of NMDA-induced GnRH release, immunocytochemistry of c-fos protein (FOS) was used for detection of neurons activated by NMDA administration. In both normal male and HPG/POA mice, FOS expression was unchanged in GnRH cells after NMDA administration. That neurosecretory cells can respond to NMDA was shown by the induction of FOS in many CRH (corticotropin-releasing hormone) cells in the paraventricular nucleus. Immunocytochemistry of beta-Endorphin, neuropeptide Y, tyrosine hydroxylase, an enzyme marker for catecholaminergic neurons, and glutamic acid decarboxylase, an enzyme marker for GABA neurons, was combined with that for FOS in normal male mice. Many noradrenergic (NA) neurons in the locus coeruleus (32-61%), and dopaminergic (DA) neurons in the mediobasal hypothalamus (15-31%) expressed FOS after NMDA administration while FOS was only rarely induced in neurons with the other neuromodulators tested. FOS was also induced in the locus coeruleus in male (43, 54%) and female (40, 55, 69%) HPG/POA mice. In contrast, few cells of the locus coeruleus expressed FOS in normal or HPG/POA mice after saline challenge. These results suggested that NMDA did not activate GnRH cells directly, but that NA neurons in the locus coeruleus were activated by NMDA and might be involved in stimulating GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Norepinephrine neurons in mouse locus coeruleus express c-fos protein after N-methyl-D,L-aspartic acid (NMDA) treatment: relation to LH release. 168 42

Catecholamines are known to exert a central influence on the hypothalamo-hypophyseal-adrenal neuroendocrine system. The selective dopaminergic innervation of the hypothalamic paraventricular nucleus (PVN) and putative relationships between dopaminergic fibers and corticotropin releasing hormone (CRH)-synthesizing neurons were studied in the male rat by means of immunocytochemistry following the elimination of noradrenergic and adrenergic inputs to the hypothalamus. A 3.0-mm-wide coronal cut was placed unilaterally in the brain at the rostral level of the mesencephalon. All neuronal structures from the cortex to the ventral surface of the brainstem, including the ascending catecholaminergic fiber bundles were transected. This surgical intervention resulted in the accumulation of dopamine-beta-hydroxylase (DBH)-immunoreactivity in axons proximal to the cut, and an almost complete disappearance of DBH activity in those located distal to the lesion. Two weeks following the operation, DBH immunoreactivity was significantly diminished in the PVN located on the side of lesion, while tyrosine hydroxylase (TH)-immunoreactivity was present in a substantial number of fibers in the same nucleus. Both DBH- and TH-immunoreactive axons were preserved in the contralateral PVN. Simultaneous immunocytochemical localization of either DBH- or TH-IR fibers and corticotropin releasing hormone-synthesizing neurons in the hypothalami from brainstem-lesioned, colchicine treated animals revealed that the distribution of catecholaminergic fibers and CRH neurons is homologous within the PVN of the intact side. Only a few scattered DBH-immunoreactive axons were detected among CRH-producing neurons in the PVN on the side of the lesion. In contrast, many tyrosine hydroxylase containing neurons and neuronal processes were observed on the lesioned side and the TH-IR fibers established juxtapositions with CRH-synthesizing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of dopaminergic fibers with corticotropin releasing hormone (CRH)-synthesizing neurons in the paraventricular nucleus of the rat hypothalamus. 257 7

Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat. 276 Jun 6

Luteinizing hormone releasing hormone (LHRH) neurons from the preoptic area (POA)/hypothalamus of the postnatal rat were cultured for up to 7 weeks using a slice explant roller culture technique. The slices thinned to quasi-monolayers, but maintained organotypic distributions of large numbers of immunocytochemically identifiable LHRH, neurotensin, tyrosine hydroxylase, neurophysin and corticotropin releasing hormone-containing neurons. The distribution, survival and morphology of LHRH cells in co-cultures with brainstem and anterior pituitary was quantitated, and found to be similar to that observed in single cultures. LHRH fibers grew into either pituitary or brainstem tissue, however when all three tissues were co-cultured, LHRH fibers preferentially invaded the pituitary. LH immunoreactive anterior pituitary gonadotropes were maintained only in co-cultures containing POA/hypothalamic slices, and addition of an LHRH antagonist in such cultures, inhibited LH immunoreactivity in the gonadotropes. This slice explant roller culture method effectively maintains the cyto- and chemoarchitecture and functional properties of the LHRH system for long periods in vitro and should provide excellent models for studying the interactive and molecular characteristics of postnatal LHRH neurons.
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PMID:Slice cultures of LHRH neurons in the presence and absence of brainstem and pituitary. 307 35

Polysialic acid (PSA) is abundant on growing axons during brain development and down regulated on maturation. However, high amounts of this carbohydrate polymer have been found to persist in some regions of the adult rat brain including the mediobasal hypothalamus. In this study, confocal laser scanning microscopy combined with double fluorescence immunostaining was used to characterize the cellular localization of PSA throughout the median eminence and neurointermediate hypophysial lobe of adult rats. In these regions, polysialic acid-immunoreactivity (PSA-IR) generally appeared associated with fiber-like structures. Double immunostaining experiments demonstrated that, in addition to large axons of the neural lobe immunoreactive to vasopressin or oxytocin, PSA was constantly associated with fibers projecting into the intermediate hypophysial lobe immunoreactive to either gamma-aminobutyric acid (GABA) or tyrosine hydroxylase. Similarly, PSA-IR was detected on most, but not all the fibers immunoreactive to GABA or tyrosine hydroxylase dispersed throughout the neural lobe and the different layers of the median eminence. On the other hand, no PSA-IR was detected on axons immunoreactive to somatostatin or to corticotropin releasing hormone projecting throughout the median eminence, or on glial cell bodies and processes immunoreactive for glial fibrillary acidic protein (GFAP) or for vimentin dispersed throughout the median eminence and the neural lobe.
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PMID:Immunolocalization of polysialic acid in the median eminence and neurointermediate hypophysial lobe of adult rats. 789 19

Systemically administered nicotine elicits ACTH release indirectly by acting on neurons in brainstem catecholaminergic regions known to send afferent projections to the paraventricular nucleus of the hypothalamus (PVN), the site of CRH neurons involved in initiating ACTH secretion. The present study in rats examined 1) the relationship between dose-dependent expression of cFos in the PVN and that in the nucleus of the solitary tract (NTS)-A2, NTS-C2 and locus coeruleus (LC), after iv nicotine (0.045-0.18 mg/kg, administered at 0.09 mg/kg per min); 2) the dependence of PVN cFos expression on the effects of nicotine in brainstem, using the nicotinic cholinergic antagonist, mecamylamine, administered into the fourth ventricle; and 3) the extent of catecholaminergic involvement in the effect of nicotine on the PVN, measured by immunocytochemical double-labeling for cFos and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. The results showed that the magnitude of cFos expression was dependent on the dose of nicotine in all regions studied (P < 0.0006); however, at the two lowest doses, only the NTS and CRH-containing region of the PVN expressed cFos, whereas the LC and the rest of the PVN were activated only by higher doses. Nicotine also elicited a dose-dependent increase in cFos expression in the TH+ neurons of the NTS, with C2 more sensitive than A2. Interestingly, the majority of NTS neurons expressing cFos were noncatecholaminergic, implicating other transmitter systems. Fourth ventricular mecamylamine completely blocked nicotine-induced cFos expression throughout the NTS, as well as the PVN. The results provide further support for the idea that catecholaminergic afferents from the NTS, but not the LC, play a significant, albeit not an exclusive, role in the activation of the PVN in response to nicotine.
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PMID:Nicotine-induced cFos expression in the hypothalamic paraventricular nucleus is dependent on brainstem effects: correlations with cFos in catecholaminergic and noncatecholaminergic neurons in the nucleus tractus solitarius. 859 11

Antidepressant drugs have in common a delayed onset of clinical efficacy. In rats, long-term, daily administration of four different types of clinically effective antidepressant drugs results in decreased corticotropin releasing hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus (PVN). Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (Arc) projects to the PVN, we measured NPY and POMC mRNA expression in the Arc using in situ hybridization histochemistry at several time points following daily administration of four different antidepressant drugs. After 14 and 56 days of imipramine treatment, Arc NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged compared to control after one or five days of treatment. Arc POMC mRNA levels are unchanged compared to controls at 1, 5, 14, or 56 days following imipramine treatment. Unlike after imipramine, Arc NPY and POMC mRNA levels are increased significantly to 134-172% of control following 56-day treatment with the antidepressant drugs fluoxetine, phenelzine, or idazoxan. The divergent effects of imipramine vs the other 3 antidepressant drugs on Arc NPY mRNA expression are similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression levels in the locus coeruleus (LC) using the same experimental paradigm, but are different from the unidirectional depressive effects of all four drugs on CRH mRNA expression in the PVN. Thus, the Arc NPY and LC noradrenergic systems may act coordinately in mediating antidepressant effects. The present data are consistent with the delayed onset of clinical efficacy for antidepressant drugs, and suggest that Arc NPY and POMC neurotransmitter systems play a role in the pathophysiology of depression.
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PMID:Effects of long-term treatment with antidepressant drugs on proopiomelanocortin and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus of rats. 873 33

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

Compared to the outbred Wistar rat strain, the Fawn-hooded rat strain has several characteristics which suggest that the Fawn-hooded strain is hyperaroused. Fawn-hooded rats exhibit more freezing behavior in response to stress, have an increased preference for alcohol, develop adult onset hypertension, and have elevated urinary catecholamine levels. We used quantitative in situ hybridization to investigate central components of the corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and noradrenergic stress response and arousal systems in these rats. We also measured basal corticosterone levels and adrenal weights to assess tonic hypothalamic-pituitary-adrenal axis activity. Compared to Wistar rats, Fawn-hooded rats had significantly increased CRH mRNA in the central nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of the hypothalamus. Fawn-hooded rats also bad reduced AVP mRNA expression in the parvocellular cells of the hypothalamic paraventricular nucleus. There were no differences between strains in glucocorticoid receptor mRNA in the hippocampus or the paraventricular nucleus or in mineralocorticoid receptor mRNA in the hippocampus. There was also no difference between strains in tyrosine hydroxylase mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced in the Fawn-hooded rats while basal corticosterone levels were similar in the two strains, which suggests central hypoactivity of the hypothalamic-pituitary-adrenal axis in Fawn-hooded rats compared to Wistar rats. Increased CRH mRNA in the central nucleus of the amygdala and reduced tonic hypothalamic-pituitary-adrenal axis activity may play a role in the unique behavioral and physiological characteristics of Fawn-hooded rats.
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PMID:Increased mRNA for corticotrophin releasing hormone in the amygdala of fawn-hooded rats: a potential animal model of anxiety. 916 May 83

CRH occurs in the adrenal medulla of rats. We were interested to know whether CRH affects meduallary chromaffin cells in the absence of ACTH. We investigated the morphological changes of the adrenal medulla in Sprague Dawley rats with light and electron microscopy in normal rats, hypophysectomized rats, and hypophysectomized rats following injections of CRH (10 micrograms = 3 nmol for three days). Chromaffin cells were characterized by immunohistochemistry (anti-tyrosine hydroxylase). At light microscopy level chromaffin cells of hypophysectomized rats were reduced in number. On electron microscopy the number of granules and cell organelles were decreased. Following injections of CRH the medulla regained a more compact texture with cell organelles homogenously distributed, but with chromaffin granules still being reduced in number. Immunohistochemistry allowed the identification of chromaffin cells located within the adrenal cortex. In hypophysectomized rats these cells showed fewer signs of alterations compared to cells located within the medulla itself and had recovered better after treatment with CRH. In conclusion, CRH seems to exert a trophic effect on chromaffin cells in the absence of pituitary ACTH. This observation may provide further evidence for a close interaction of the two neuroendocrine stress systems.
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PMID:The effect of corticotropin-releasing hormone (CRH) on the adrenal medulla in hypophysectomized rats. 947 37


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