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)

It is known that norepinephrine (NE) is important in the neuroendocrine control of pituitary gonadotropin II (GTH-II) and growth hormone (GH) release but very little is known about the factors regulating NE neurons in the goldfish brain. Female gonad-intact goldfish were implanted intraperitoneally (100 micrograms/g) with testosterone (T) or estradiol (E2) to elevate serum steroid levels. High-performance liquid chromatography measurements showed that steroid implantation had no effect on NE content in the telencephalon, including preoptic area (TEL-POA), or the hypothalamus (HYP). The turnover rate of NE was estimated from the rate of depletion of NE content from tissues following inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (240 micrograms/g). The present study demonstrates that E2 can decrease NE turnover rates in TEL-POA and HYP of sexually regressed goldfish (August). The results in recrudescent fish (November), however, indicate a more complex interaction of E2 with NE neurons since E2 increased NE turnover in TEL-POA and HYP in these animals. Testosterone (T) has less prominent effects on NE turnover rates in TEL-POA and HYP; the only significant effect of T-implantation was a small reduction of NE turnover in the TEL-POA of sexually recrudescent fish. Elevation of endogenous brain GABA concentrations by injection of the GABA transaminase inhibitor, gamma-vinyl-GABA (300 micrograms/g), significantly reduced NE turnover in TEL-POA. These data demonstrate that goldfish NE neurons in the TEL-POA are sensitive to regulation by changes in circulating sex steroids and by increases in brain GABA.
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PMID:Norepinephrine turnover in the goldfish brain is modulated by sex steroids and GABA. 825 2

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.
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PMID:Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system. 898 82

We studied the effects of treatment with (-)-deprenyl, a monoamine oxidase B inhibitor, on plasma levels of insulin-like growth factor-I (IGF-I) (as indicator of growth hormone (GH) secretion), levels of monoamines and their metabolites, and the activity and content of tyrosine hydroxylase - the rate-limiting enzyme in the biosynthesis of catecholamines - in the hypothalamus and hypophysis of old male rats. Male Wistar rats (22 months old) were treated with 2 mg deprenyl/kg body weight s.c. three times a week for 2 months. At the end of the treatment period, blood was collected for measurement of plasma IGF-I levels by radioimmunoassay (RIA). The concentrations of dopamine, serotonin (5-HT) and their main metabolites were determined by high performance liquid chromatography (HPLC) with electrochemical detection, and the tyrosine hydroxylase content in hypothalamus and hypophysis was determined by enzyme-linked immunoabsorbent assay (ELISA). (-)-Deprenyl treatment produced a pronounced increase in dopamine and 5-HT in both the hypothalamus and hypophysis (P < 0.01). The main dopaminergic metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), decreased in hypothalamus but not in hypophysis, and treatment had no effect on the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA). The tyrosine hydroxylase activity and tyrosine hydroxylase content increased in hypothalamus and hypophysis (P < 0.05). In the hypophysis the increase in tyrosine hydroxylase activity was consistent with the increase in tyrosine hydroxylase amount. Moreover, (-)-deprenyl treatment restored the IGF-I plasma levels in old rats to a concentration similar to those found in young animals. Postulated anti-aging effects of (-)-deprenyl could hence be due to restoration of hypothalamic hormones such as GH.
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PMID:(-)-Deprenyl treatment restores serum insulin-like growth factor-I (IGF-I) levels in aged rats to young rat level. 920 May 62

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.
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PMID:Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. 922 69

The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin- and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormone-containing neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.
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PMID:Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. 941 31

In transgenic growth-retarded (Tgr) rats, expression of human growth hormone (hGH) is targeted to hypothalamic GH-releasing hormone (GHRH) neurones. In these rats, GHRH is reduced and somatostatin expression is increased, resulting in secondary GH deficiency and dwarfism. Tgr rats also show reduced pituitary prolactin (PRL), which may reflect an additional lactogenic feedback action of the hGH transgene, analogous to that in mice transgenic for peripheral hGH which show enhanced dopamine (DA) and tyrosine hydroxylase (TH) expression in the hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones that inhibit PRL secretion. The present study examined DA histofluorescence and TH immunoreactivity in Tgr rats, and also in dw/dw rats, a dwarf strain with primary pituitary GH but not PRL deficiency. Radioimmunoassay confirmed a significant decrease in total pituitary PRL content in Tgr rats, but showed a marked increase in total pituitary PRL in dw/dw rats. Despite their PRL deficiency, Tgr rats showed qualitatively increased TIDA histofluorescence and TH immunoreactivity compared with AS control rats, though the total number of detectable TH-positive TIDA neurones was similar for Tgr and AS. In contrast, dw/dw rats showed increased numbers of TH-immunoreactive TIDA neurones whilst TIDA fluorescence was unchanged, and these findings were not affected in dw/dw rats given bovine GH (200 microg/d s.c. for 7 d). These results suggest that reduced PRL in Tgr rats is due to a local lactogenic feedback effect of hGH to stimulate TIDA neurones. The complex changes in TIDA neurones probably reflect a combination of increased lactogenic feedback in Tgr rats, with an increased (Tgr) or decreased (dw/dw) somatogenic feedback on GHRH neurones, some of which coexpress TH. Thus, the unchanged number of TIDA neurones in Tgr rats may result from hGH stimulation of TH and DA, but a reduction in GHRH-producing cells, whereas increased TIDA neurones in dw/dw rats suggests a stimulation by endogenous PRL with an increased GHRH cell complement due to GH deficiency. These findings therefore indicate that differences in lactogenic feedback in these dwarf rat models are reflected in marked differences in their hypothalamic TIDA neurones.
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PMID:Differential regulation of hypothalamic tuberoinfundibular dopamine neurones in two dwarf rat models with contrasting changes in pituitary prolactin. 1020 19

Bronchial endocrine neoplasms causing acromegaly due to ectopic production of growth hormone (GH)-releasing hormone (GHRH) have been reported. We describe the case of a 39-year-old man with clinical and biochemical acromegaly. Magnetic resonance imaging revealed an enlarged pituitary, which was confirmed histologically to harbour somatotroph hyperplasia. Further investigations identified a circumscribed central mass in the right lung which was surgically resected and histologically confirmed to be an endocrine tumour with strong immunopositivity for GHRH, synaptophysin and chromogranin; the lesion also exhibited mild positivity for peptide YY, calcitonin gene-related peptide (CGRP), glucagon-like peptide (GLP)-1, corticotrophin-releasing hormone (CRH), tyrosine hydroxylase, vasoactive intestinal peptide (VIP) and enkephalin. S100 protein was identified in stellate cells surrounding nests of epithelial tumour cells. The MIB-1 antibody labelled about 10% of the tumour cells. We established that the tumour not only produced GHRH but the GHRH-receptor (GHRH-R) as well. GHRH and GHRH-R mRNA were identified and the latter was characterized as two variants, a full-length transcript and a truncated splice variant that has been described in human pituitary somatotroph adenomas. We suggest that GHRH expression by this tumour and the presence of its receptor may be responsible for enhanced growth. The expression of a truncated splice variant that is unable to transduce GHRH signalling may be implicated in the less aggressive behaviour of well-differentiated endocrine tumours that produce GHRH compared with small-cell lung carcinomas that are very responsive to GHRH growth stimulation.
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PMID:Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform expression in ectopic acromegaly. 1145 63

Differentiation of hypophysiotropic neurones that regulate the secretion of growth hormone (GH) and prolactin is influenced by GH and prolactin. Genetic GH and prolactin deficiency in mutant rodent models such as the Ames dwarf (df/df) mouse results in an increase in the number of GH-stimulatory GH-releasing hormone (GHRH) neurones and a reduction of prolactin-inhibitory tuberoinfundibular dopaminergic (TIDA) neurones in the arcuate nucleus during postnatal development. The present study tested the hypothesis that these concomitant changes in numbers of tyrosine hydroxylase (TH)- and GHRH-immunoreactive neurones in df/df hypothalamus might represent a neuronal population of fixed number that undergoes a partial change in phenotype during postnatal development. To evaluate this possibility, the postnatal reduction of the df/df TIDA population was prevented by administering prolactin neonatally to preserve TH phenotype; dwarf and normal sibling mice were treated with daily injections of ovine prolactin or vehicle starting at postnatal day 12 and continuing for 30 days. Following this treatment, numbers of arcuate neurones containing GHRH or TH, or both, were quantified using immunocytochemistry. It was hypothesized that prolactin preservation of TH-immunoreactive cell number would be accompanied by either a decrease in the GHRH-producing population or an increase in numbers of cells producing both TH and GHRH. In prolactin-treated normal (DF/df) mice, numbers of arcuate TH-immunoreactive neurones were similar to those in vehicle-treated normals. Numbers of TH-positive neurones in prolactin-treated dwarfs were higher than in vehicle-treated dwarfs, and did not differ from numbers in DF/df. Numbers of GHRH-immunoreactive cells in vehicle-treated df/df were higher than in vehicle-treated DF/df, and were not different in prolactin-treated groups of either dwarf or normal mice. Neurones containing both TH and GHRH constituted 15% of the TH population, and 76% of the GHRH population, in control normal mice; in control dwarfs, double-labelled cells were 9.3% of TH and 9.9% of GHRH. Numbers of cells immunoreactive for both TH and GHRH were not affected by prolactin treatment in either mouse type. These results demonstrate that the increase in number of GHRH-expressing neurones in the df/df arcuate nucleus does not occur at the expense of the TH phenotype, and that this increase is not influenced by prolactin feedback. Although coexpression of TH and GHRH in a subpopulation indicates that TIDA and GHRH populations are not exclusive, they appear to be influenced independently by prolactin and GH signals during development.
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PMID:Growth hormone-releasing hormone-producing and dopaminergic neurones in the mouse arcuate nucleus are independently regulated populations. 1258 17

We investigated the proteome of the anterior pituitary gland (AP) in a species in which the genome has been sequenced. Subcellular fractions of APs from 2-month-old male mice were prepared for protein denaturation, treatment with trypsin and analyses utilizing micro liquid chromatography tandem mass spectrometry and the database search software SEQUEST. In the nuclear, non-nuclear 100,000 g and cytosolic fractions, we identified 49, 36 and 68 different proteins, respectively. A total of 115 distinct proteins were detected. We identified growth hormone, prolactin, pro-opiomelanocortin, the alpha-subunit for the glycoprotein hormones, and luteinizing hormone-beta. Groups of other identified proteins included hormone-processing, secretion granule-associated, non-hormonal endoplasmic reticulum-associated, calcium-binding, protein kinase C-associated, histones, non-histone chromosomal, other RNA-binding, heterogeneous nuclear ribonucleoproteins, splicing factors, helicases, lamins, ribosomal, microtubule-associated, microfilament-associated, adenosine triphosphate- and guanosine triphosphate-associated, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation, enzymes in glycolysis and the tricarboxylic and urea cycles and the pentose phosphate path, heat-shock, glutathione-associated, peroxidases, ubiquitin-associated, catabolic, protease inhibitors, other, and blood proteins. The 115 proteins reported in this study and the 145 proteins reported in a previous study on the AP of the adult male Golden Syrian hamster are compared and form a foundation for defining the proteome in normal adult male AP.
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PMID:Mouse anterior pituitary gland: analysis by ion trap mass spectrometry. 1610 33

Ghrelin is a hormone that stimulates growth hormone secretion and signals energy insufficiency via interaction with its receptor, the growth hormone secretagogue receptor (GHSR). The GHSR is located in both the central nervous system and the periphery. Its distribution in the CNS, as assessed by in situ hybridization histochemistry (ISHH), has been described previously in a few mammalian species, although these studies were limited by either the detail provided or the extent of the regions examined. In the present study, we systematically examined the distribution of GHSR mRNA in the adult rat and mouse brains and cervical spinal cords by using ISHH with novel cRNA probes specific for the mRNA encoding functional GHSR (the type 1a variant). We confirmed GHSR mRNA expression in several hypothalamic nuclei, many of which have long been recognized as playing roles in body weight and food intake. GHSR also was found in several other regions previously unknown to express GHSR mRNA, including many parasympathetic preganglionic neurons. Additionally, we found GHSR mRNA within all three components of the dorsal vagal complex, including the area postrema, the nucleus of the solitary tract, and the dorsal motor nucleus of the vagus. Finally, we examined the coexpression of GHSR with tyrosine hydroxylase and cholecystokinin and demonstrate a high degree of GHSR mRNA expression within dopaminergic, cholecystokinin-containing neurons of the substantia nigra and ventral tegmental area.
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PMID:Expression of ghrelin receptor mRNA in the rat and the mouse brain. 1632 Feb 57


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