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)

Infusion of 2 nmol atrial natriuretic factor (ANF) into the third cerebroventricle of conscious, orchidectomized male rats results in a significant inhibition of prolactin (PRL) secretion. This effect is prevented by prior treatment with the dopamine receptor antagonist, domperidone. Furthermore, domperidone reverses the inhibitory effect when given after ANF infusion. The PRL-inhibiting effect is absent as well following inhibition of tyrosine hydroxylase activity. These results suggest that ANF acts centrally at least in part via an interaction with endogenous dopaminergic systems and further suggests potent neuromodulatory actions of the peptide within the hypothalamus.
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PMID:Evidence for a dopaminergic mechanism for the prolactin inhibitory effect of atrial natriuretic factor. 289 10

Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: (1) diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; (2) mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; (4) immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; (5) ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; (6) preliminary biochemical studies revealed increased beta-endorphines in thalamus and cerebellum; (7) peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance.
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PMID:Neuropathology of Rett syndrome. 290 May 87

An attempt was made to correlate the physiological or the dimethylbenz(a)anthracene (DMBA)-enhanced serum prolactin (PRL) surge, which occurs in the afternoon of proestrus in female Sprague-Dawley (SD) rats, with physiological or pathological changes in two biochemical estimates of the tuberoinfundibular dopaminergic (TIDA) neuron activity. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations as well as tyrosine hydroxylase (TH) activity were measured in the median eminence (ME) of control or DMBA-pretreated SD rats throughout the estrous cycle in relation to PRL secretion. In both groups of females, while the DA content was fairly constant, the DOPAC content and TH activity in the ME fluctuated markedly throughout the estrous cycle. Thus, in control animals, the DOPAC content, DOPAC/DA ratio and TH activity which were stable on the days of diestrus and morning of proestrus were markedly decreased at noon and early afternoon when serum PRL levels began to rise. Later in the afternoon of proestrus, when serum PRL levels were maximal, there was a marked but transient increase in the DOPAC content and DOPAC/DA ratio as well as a brief surge in TH activity. In the evening of the same day, when serum PRL returned to basal levels, the DOPAC content, DOPAC/DA ratio and TH activity were low. Finally on estrus morning, the DOPAC content, DOPAC/DA ratio and TH activity increased again to reach the diestrus levels. In DMBA-pretreated females, similar fluctuations in TIDA neuronal activity occurred during the estrous cycle, but the dynamics of these changes was altered: the DOPAC/DA ratio and TH activity first showed a marked increase in the morning of proestrus day, before decreasing dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in tuberoinfundibular dopaminergic neuron activity during the rat estrous cycle in relation to the prolactin surge: alteration by a mammary carcinogen. 290 62

Indirect immunofluorescence histochemistry was used to study the relation among GABAergic, catecholaminergic, cholinergic, and peptidergic neurons in the rat mediobasal hypothalamus. By employing a direct double-labelling procedure using sheep antiserum against glutamic acid decarboxylase (GAD), mouse monoclonal and rabbit antibodies to neurotensin (NT) and rabbit antisera to tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), galanin (GAL), growth hormone-releasing factor (GRF), or somatostatin (SOM), it was demonstrated that GAD-positive fibers and terminals in the external part of the median eminence co-contained immunoreactivity for TH, NT, GAL or GRF, but not for SOM. In the internal part of the median eminence-infundibular stalk, GAD-positive/NT-, GAL-, and GRF-negative and GAD-positive/TH-positive fiber plexa were shown. When a recently developed direct triple-labelling procedure with biotin-conjugated mouse secondary antibodies in conjunction with diethylaminocoumarin (DAMC)-conjugated avidin was employed, presence of GAD/GAL/NT- as well as GAD/GRF/NT-containing varicosities could be demonstrated close to hypophysial portal vessels. In colchicine-pretreated animals, GAD was shown to coexist with TH, NT, or GAL in cell bodies in both the dorsomedial and ventrolateral domains of the arcuate nucleus, but with GRF only in the ventrolateral division. ChAT-positive neurons in the ventrolateral region were also TH-positive. In the ventrolateral arcuate nucleus, triple-labelling followed by elution-restaining showed GAD/NT/GAL/TH-immunoreactivities in the same cells. Similarly, double-labelling with two following elution-restaining steps showed several NT/GAL/GRF/TH-containing cell bodies in this part of the arcuate nucleus. GAD-positive cells in the anterior hypothalamic periventricular area and fibers in the pituitary neurointermediate lobe were also TH-positive. The results demonstrate complex patterns of storage of chemical messengers in neurons of the arcuate nucleus-median eminence complex. Possible neuroendocrine interactions of these systems in the control of prolactin and growth hormone secretion are discussed.
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PMID:Peptide- and transmitter-containing neurons in the mediobasal hypothalamus and their relation to GABAergic systems: possible roles in control of prolactin and growth hormone secretion. 290 36

The roles of prolactin (PRL) and the ovarian hormones, estradiol and progesterone, in the control of tuberoinfundibular dopaminergic neurons of aged female rats were investigated. The in situ molar activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-dihydroxyphenylalanine in the median eminence following the administration of a L-dihydroxiphenylalanine decarboxylase inhibitor. The TH mass was measured by an immunoblot assay using rat TH as the standard. Pituitary implants in aged ovariectomized animals resulted in a significant increase in the median eminence of both the mass and in situ molar activity of TH. When circulating PRL of aged rats was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that of animals treated with preimmune serum. In aged ovariectomized rats treated with both estradiol and progesterone, the in situ molar activity of TH increased significantly compared to animals treated only with the solvent vehicle, estradiol, or progesterone. The stimulatory effect of estradiol and progesterone appeared to be mediated through a mechanism that did not involve PRL, since neutralization of circulating PRL failed to prevent an increase in TH activity in estradiol-progesterone-treated animals. None of these treatments affected the in situ activity of TH in the superior cervical ganglion. We conclude that PRL as well as combined estradiol-progesterone treatment have important roles in the maintenance of TH activity in aged tuberoinfundibular dopaminergic neurons.
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PMID:Mass and activity of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons of the aged brain. Control by prolactin and ovarian hormones. 290 99

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.
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PMID:Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat. 291 39

Diestrous female rats were exposed to the smoke from one to four cigarettes. Exposure to unfiltered cigarette smoke produced dose- and time-dependent reductions of catecholamine levels and dose- and time-dependent increase in catecholamine utilization in the various hypothalamic and preoptic dopamine and noradrenaline nerve terminal systems. These effects were counteracted by pretreatment with the ganglion blocking agent mecamylamine (1 mg/kg). Exposure to cigarette smoke was also found to produce a dose- and time-dependent inhibition of serum prolactin, LH and FSH levels which was counteracted by pretreatment with mecamylamine. Exposure to the smoke from one cigarette (but not from four cigarettes) increased serum TSH levels. In combination with tyrosine hydroxylase inhibition the exposure to cigarette smoke produced a dose- and time-dependent inhibition of plasma ACTH levels, an action which was counteracted by pretreatment with mecamylamine. The results demonstrated a sex difference (cf. Anderson et al. 1985c), in the nicotine-induced changes of TSH and ACTH secretion despite a general increase in hypothalamic and preoptic dopamine and noradrenaline utilization in both the male and the diestrous female rat. The differences in the neuroendocrine actions of acute intermittent exposure to cigarette smoke in the diestrous rat and the normal male rat are discussed.
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PMID:Effects of acute intermittent exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on neuroendocrine function in the diestrous rat. 296 98

Male rats were exposed to the smoke from 2 cigarettes every morning for a total-period of 9 days. The next day they were decapitated immediately after the exposure to the smoke from 4 cigarettes (Kentucky reference IR-1 type) burned at 30-min intervals. Control animals were exposed to air alone or to nicotine-free cigarette smoke (Cambridge glass fibre filters). In contrast to chronic exposure to filtered smoke, exposure to unfiltered smoke resulted in a 10% increase in catecholamine (CA) levels (quantitative histofluorimetry) within the lateral palisade zone, the posterior periventricular hypothalamic nucleus and within the dorsomedial hypothalamic nucleus. There was also an increase in amine turnover (tyrosine hydroxylase inhibition by alpha-methyl-dl-p-tyrosine methylester; alpha MT) in the dopamine (DA) systems of the medial and lateral palisade zones and in the periventricular noradrenaline (NA) hypothalamic systems. Chronic exposure to unfiltered cigarette smoke resulted in reductions of prolactin, LH and FSH levels (radioimmunoassay). Following alpha MT treatment chronic exposure to unfiltered cigarette smoke still led to reduced prolactin serum levels. In addition an increased vasopressin serum concentration was found. The effects of chronic exposure to cigarette smoke on neuroendocrine function and on hypothalamic CA systems are suggested to be mediated via nicotine. Combined with the results from a previous study the present results indicate that tolerance does not develop with regard to the inhibitory effects of exposure to cigarette smoke on prolactin, LH and FSH secretions. The same is true for the stimulatory effects on the tubero-infundibular DA neurons and the periventricular NA systems. But chronic exposure to cigarette smoke seemed to induce tolerance with regard to its stimulatory effects on subependymal, dorsomedial and paraventricular hypothalamic NA systems and on corticosterone release.
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PMID:Effects of chronic exposure to cigarette smoke on amine levels and turnover in various hypothalamic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat. 300 59

Most of what is known about dopamine (DA)-containing neurons in the brain has been learned from studies on the nigrostriatal system, although it is misleading to consider a neuron in this system as a "model" for other DA neurons in the brain. In this presentation the properties of nigrostriatal DA neurons are compared with those hypothalamic DA neurons that comprise the tuberoinfundibular system. These latter neurons, which have cell bodies in the arcuate nucleus and short axons which terminate in the median eminence, function to inhibit the release of prolactin from the anterior pituitary. The activities of the nigrostriatal and tuberoinfundibular DA neurons were estimated biochemically by measuring the rates of synthesis (accumulation of DOPA after the administration of a decarboxylase inhibitor, NSD 1015), turnover (decline of DA after the administration of a tyrosine hydroxylase inhibitor, alpha-methyltyrosine) and metabolism (concentrations of dihydroxyphenylacetic acid) of DA in regions of the brain that contain the terminals of these neurons (striatum and median eminence, respectively). Tuberoinfundibular DA neurons differ from nigrostriatal DA neurons in that the former neurons: (1) are not directly regulated by DA receptor-mediated mechanisms, (2) are stimulated by prolactin, (3) exhibit a sexual difference with activity being 2-3 times greater in females and (4) are inhibited by afferent neuronal circuits that are activated by suckling and restraint stress.
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PMID:Stress, prolactin and hypothalamic dopaminergic neurons. 330 8

The present work examines the ability of prolactin to enter the CNS of the rat and effect its feedback stimulation of dopamine release prior to the appearance of prolactin receptors in choroid plexus (i.e., 10 days postnatal). An inhibitor of tyrosine hydroxylase was used to allow the assessment of dopamine turnover separate from synthesis and transport of the amine. Chronic but not acute hyperprolactinemia resulted in increased dopamine release relative to vehicle-treated controls, as shown by diminished fluorescence intensity in the median eminence. These results indicate that activation of the prolactin short-loop feedback system occurs by 10 days postnatal, prior to the appearance of prolactin receptors at the choroid plexus.
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PMID:Prolactin causes increased turnover of dopamine in 10-day-old rat median eminence. 345 64


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