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)

The preoptic area contains most of the luteinizing hormone releasing hormone immunoreactive neurons and numerous monoaminergic afferents whose cell origins are unknown in sheep. Using tract tracing methods with a specific retrograde fluorescent tracer, fluorogold, we examined the cells of origin of afferents to the medial preoptic area in sheep. Among the retrogradely labeled neurons, immunohistochemistry for tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase, and serotonin was used to characterize catecholamine and serotonin fluorogold labeled neurons. Most of the afferents came from the ipsilateral side to the injection site. It was observed that the medial preoptic area received major inputs from the diagonal band of Broca, the lateral septum, the thalamic paraventricular nucleus, the lateral hypothalamus, the area dorsolateral to the third ventricle, the perimamillary area, the amygdala, and the ventral part of the hippocampus. Other numerous, scattered, retrogradely labeled neurons were observed in the ventral part of the preoptic area, the vascular organ of the lamina terminalis, the ventromedial part of the hypothalamus, the periventricular area, the area lateral to the interpeduncular nucleus, and the dorsal vagal complex. Noradrenergic afferents came from the complex of the locus coeruleus (A6/A7 groups) and from the ventro-lateral medulla (group A1). However, dopaminergic and adrenergic neuronal groups retrogradely labeled with fluorogold were not observed. Serotoninergic fluorogold labeled neurons belonged to the medial raphe nucleus (B8, B5) and to the serotoninergic group situated lateral to the interpeduncular nucleus (S4). In the light of these anatomical data we hypothesize that these afferents have a role in the regulation of several functions of the preoptic area, particularly those related to reproduction. Accordingly these afferents could be involved in the control of luteinizing hormone releasing hormone (LHRH) pulsatility or of preovulatory LHRH surge.
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PMID:Neuronal projections to the medial preoptic area of the sheep, with special reference to monoaminergic afferents: immunohistochemical and retrograde tract tracing studies. 849 68

The enzyme aromatase converts testosterone (T) into 17 beta-estradiol and plays a pivotal role in the control of reproduction. In particular, the aromatase activity (AA) located in the preoptic area (POA) of male Japanese quail is a limiting step in the activation by T of copulatory behavior. Aromatase-immunoreactive (ARO-ir) cells of the POA are specifically localized within the cytoarchitectonic boundaries of the medial preoptic nucleus(POM), a sexually dimorphic and steroid-sensitive structure that is a necessary and sufficient site of steroid action in the activation of behavior. Stereotaxic implantation of aromatase inhibitors in but not around the POM strongly decreases the behavioral effects of a systemic treatment with T of castrated males. AA is decreased by castration and increased by aromatizable androgens and by estrogens. These changes have been independently documented at three levels of analysis: the enzymatic activity measured by radioenzymatic assays in vitro, the enzyme concentration evaluated semi-quantitatively by immunocytochemistry and the concentration of its messenger RNA quantified by reverse transcription-polymerase chain reaction (RT-PCR). These studies demonstrate that T acting mostly through its estrogenic metabolites regulates brain aromatase by acting essentially at the transcriptional level. Estrogens produced by central aromatization of T therefore have two independent roles: they activate male copulatory behavior and they regulate the synthesis of aromatase. Double label immunocytochemical studies demonstrate that estrogen receptors(ER) are found in all brain areas containing ARO-ir cells but the extent to which these markers are colocalized varies from one brain region to the other. More than 70% of ARO-ir cells contain detectable ER in the tuberal hypothalamus but less than 20% of the cells display this colocalization in the POA. This absence of ER in ARO-ir cells is also observed in the POA of the rat brain. This suggests that locally formed estrogens cannot control the behavior and the aromatase synthesis in an autocrine fashion in the cells where they were formed. Multi-neuronal networks need therefore to be considered. The behavioral activation could result from the action of estrogens in ER-positive cells located in the vicinity of the ARO-ir cells where they were produced (paracrine action). Alternatively, actions that do not involve the nuclear ER could be important. Immunocytochemical studies at the electron microscope level and biochemical assays of AA in purified synaptosomes indicate the presence of aromatase in presynaptic boutons. Estrogens formed at this level could directly affect the pre-and post-synaptic membrane or could directly modulate neurotransmission namely through their metabolization into catecholestrogens (CE) which are known to be powerful inhibitors of the catechol- omicron - methyl transferase (COMT). The inhibition of COMT should increase the catecholaminergic transmission. It is significant to note, in this respect, that high levels of 2-hydroxylase activity, the enzyme that catalyzes the transformation of estrogens in CE, are found in all brain areas that contain aromatase. On the other hand, the synthesis of aromatase should also be controlled by estrogens in an indirect, transynaptic manner very reminiscent of the way in which steroids indirectly control the production of LHRH. Fibers that are immunoreactive for tyrosine hydroxylase (synthesis of dopamine), dopamine beta-hydroxylase (synthesis of norepinephrine) or vasotocine have been identified in the close vicinity of ARO-ir cells in the POM and retrograde tracing has identified the origin of the dopaminergic and noradrenergic innervation of these areas. A few preliminary physiological experiments suggest that these catecholaminergic inputs regulate AA and presumably synthesis.
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PMID:Effects of testosterone and its metabolites on aromatase-immunoreactive cells in the quail brain: relationship with the activation of male reproductive behavior. 860 40

Mating with intromission induces a prolonged preovulatory LH surge in the estrous female ferret but inhibits LH secretion in the male. We used the dual immunocytochemical localization of Fos (as a marker of neural activation) and tyrosine hydroxylase (TH) to determine whether neurons containing norepinephrine or other catecholamines are activated after mating. Breeding male ferrets were allowed to intromit with estrous females; both animals were perfused 90 min after the onset of intromission. Other male and female ferrets were perfused 90 min after being placed in a cage in which an opposite-sex ferret in breeding condition had previously been housed for 48 h. Control ferrets of each sex were perfused 90 min after being placed alone in a clean testing cage. Mating with intromission significantly augmented the percentage of TH-immunoreactive (TH-IR) neurons colabeled with nuclear Fos-like immunoreactivity (Fos-IR) in both the A6 and the rostral A2 midbrain catecholamine cell groups in females, but not males. Exposure to chemosensory cues alone also increased the percentage of Fos-IR TH neurons in the rostral A2, but not the A6, cell group in females. Chemosensory cues alone did not affect the percentage of double-labeled neurons in either cell group in males. These activated midbrain TH-IR neurons are most likely noradrenergic, and their activation in estrous females may facilitate the mediobasal hypothalamic release of LHRH required for the preovulatory LH surge. In both sexes, mating with intromission, but not chemosensory cues alone, augmented the percentage of periglomerular TH-IR neurons in the main olfactory bulb (MOB) that were colabeled with Fos-IR. These activated TH-IR neurons in the MOB are most likely dopaminergic. Their role in the neural response to mating is currently unknown.
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PMID:Sexually dimorphic activation of midbrain tyrosine hydroxylase neurons after mating or exposure to chemosensory cues in the ferret. 916 92

In mammalian species, ovulation occurs following a massive release of hypothalamic gonadotropin-releasing hormone (GnRH). Several chemicals, including norepinephrine (NE) and neuropeptide Y (NPY), are responsible for the initiation and/or magnitude and duration of this pre-ovulatory GnRH surge. In the central nervous system, NE neural cell bodies are located in the brainstem; some are co-localized with NPY neurons and/or co-express the NE transporter (NET) gene which dictates NET protein production. The activity of NET at NE terminals is critical for synaptic NE function. In the rabbit, coitus induces a hypothalamic NE release which precedes the GnRH surge. We hypothesize that the coital stimulus is transmitted to the brainstem and transformed and integrated into GnRH-stimulating signals via NE, NET and/or NPY. However, very little is known about the distribution of cells expressing NET, NPY and tyrosine hydroxylase (TH, the rate-limiting enzyme of NE synthesis) in this species. Therefore, we utilized the sensitive in situ hybridization technique to identify the presence of these messages in conjunction with the location of NE cells, the latter being marked by dopamine beta-hydroxylase (DBH), the specific enzyme for NE synthesis. Three non-mated New Zealand White does were perfused with 4% paraformaldehyde and their brainstems were sectioned at 20-micron thick between 2 mm caudal to the obex and the rostral pons. Serial sections were immunohistochemically stained for DBH and hybridized with rabbit-specific TH and NET cRNAs and a human NPY probe. The data suggest that several DBH-positive areas in the medulla expressed one or more messages, i.e. the lateral tegmentum (A1) and the nucleus of the solitary tract (A2) expressed all three mRNAs, the area postrema (AP) contained NET and TH mRNAs but not NPY cells. In the pons, the locus coeruleus (LC), subnucleus of coeruleus (LCs) and lateral tegmental nuclei (A5) expressed NET and TH mRNAs but contained little or no NPY message. The distribution patterns of TH and NET appeared to be similar in the LC, LCs, A2 and AP.
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PMID:Topographic comparison of the expression of norepinephrine transporter, tyrosine hydroxylase and neuropeptide Y mRNA in association with dopamine beta-hydroxylase neurons in the rabbit brainstem. 933 34

The central noradrenergic system has a major regulatory role on gonadotropin-releasing hormone/luteinizing hormone (GnRH/LH) secretion in rabbits. Exogenous administration of norepinephrine (NE) alters GnRH/LH release in a sex steroid-dependent manner, i.e. NE stimulates GnRH/LH release in oestrogen-primed ovariectomized (OVX) animals but not in non-primed individuals. To investigate how gonadal steroids influence noradrenergic neuronal activities in the locus coeruleus (LC), mRNA levels of tyrosine hydroxylase (TH) and NE transporter (NET), two key factors regulating NE synthesis and uptake, were compared 3 weeks after gonadectomy (GDX). Intact male (n = 5) and female (n = 6) New Zealand White rabbits were sacrificed along with castrated males (n = 4) and OVX females (n = 5). The brainstem from each individual was sectioned and the LC was punched for detection of TH and NET mRNA levels using the ribonuclease protection assay (RPA). Trunk blood was collected to determine immunoactive serum LH values. Levels of LH were elevated in both males and females after GDX. Luteinizing hormone concentrations averaged 0.10 +/- 0.05 ng/ml in intact males vs 1.64 +/- 0.31 ng/ml in castrated males (P < 0.01) and 0.30 +/- 0.08 ng/ml in intact vs 9.80 +/- 3.50 ng/ml in OVX females (P < 0.05), respectively. Removal of the gonads also increased TH mRNA levels in the LC in both males and females. In intact males, TH mRNA levels were 0.796 +/- 0.181 pg/microgram total RNA, whereas in castrates mRNA levels averaged 1.667 +/- 0.345 pg/microgram total RNA (P < 0.05). In intact females, TH mRNA levels were 0.617 +/- 0.054 pg/microgram total RNA while the OVX group averaged 1.084 +/- 0.202 pg/microgram total RNA (P < 0.05). Similar increases in NET mRNA were noted after GDX in both sexes. In males, NET mRNA levels were 1.461 +/- 0.401 pg/microgram total RNA in intacts vs 3.666 +/- 0.649 pg/microgram total RNA in castrates (P < 0.05). In females, NET mRNA levels averaged 1.336 +/- 0.212 pg/microgram total RNA and 3.297 +/- 0.835 pg/microgram total RNA in the intact and OVX groups, respectively (P < 0.05). The data indicate that GDX enhances gene expression of both TH and NET. The results support the hypothesis that the feedback regulation of sex steroids on LH secretion in rabbits of both sexes involves transcriptional/translational processes of at least TH and NET in brainstem NE cells.
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PMID:Gonadectomy alters tyrosine hydroxylase and norepinephrine transporter mRNA levels in the locus coeruleus in rabbits. 935 45

We unilaterally destroyed the nasal radix of rat embryos on day 15.5 of gestation (E15.5) in utero so as to block the olfactory inputs to the ipsilateral forebrain vesicle. The embryonic brains were examined after 6 days' survival (E21.5). In the deafferented half of the brain, LHRH neurons were significantly reduced in number, indicating the successful blocking of the olfactory input. On the deafferented side, the olfactory bulb failed to develop, and the telencephalic hemisphere, small in size, accompanied various histogenetic retardations in the primary olfactory cortex, in the cortical plate, and in the hippocampal formation. The striatum revealed remarkable structural differences between the ipsilateral and contralateral sides: on the ipsilateral side, the striatum was small in size and displayed numerical reductions of immunoreactive tyrosine hydroxylase (TH) fibers and substance P (SP) neurons in comparison with those in the contralateral one; in the substantia nigra, TH neurons and SP fibers were less numerous on the deafferented side. There were no remarkable differences in the distribution of TH neurons in the hypothalamus. In view of these sequential histogenetic alterations, it can be assumed that the olfactory inputs play a key role in the telencephalic morphogenesis.
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PMID:Destruction of olfactory inputs affects the morphogenesis of the telencephalon in rats. 941 37

Orphanin FQ (OFQ) is a novel heptadecapeptide whose structure resembles that of dynorphin A1-17. Its receptor shares appreciable homology with mu-, delta- and kappa-opioid receptors, and is highly expressed in the hypothalamus. The present study examined the effects of OFQ on neurons within the arcuate nucleus (ARC) of the mediobasal hypothalamus, using intracellular recordings from coronal slices. In current clamp, OFQ produced a hyperpolarization of ARC neurons, including those immunopositive for beta-endorphin, tyrosine hydroxylase and gonadotropin-releasing hormone. This hyperpolarization was dose-dependent, insensitive to antagonism by naloxone and was associated with a decrease in input resistance. In voltage clamp, OFQ produced an outward current associated with an increase in conductance. Varying the extracellular K+ concentration shifted the reversal potential for the OFQ response to the degree predicted by the Nernst equation. Furthermore, barium chloride markedly attenuated both the OFQ-induced hyperpolarization and decrease in input resistance. Administration of maximally effective concentrations of OFQ, followed by coadministration of maximal concentrations of either OFQ and the mu-opioid receptor agonist DAMGO or OFQ and the GABAB receptor agonist baclofen produced additive hyperpolarizations and outward currents. If DAMGO was applied first, followed by the coadministration of DAMGO and OFQ, then the responses were occluded. Taken together, these results indicate that OFQ inhibits beta-endorphin neurons, as well as A12 dopamine and GnRH neurosecretory cells, within the ARC by activating a subset of inwardly-rectifying K+ channels. This suggests that OFQ is not only an antiopioid peptide, but that it also modulates the hypothalamo-pituitary axis and, ultimately, reproductive behavior.
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PMID:The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance. 950 37

It has been recently demonstrated that nitric oxide (NO), a free radical gas which may act as neurotransmitter in the brain, can stimulate the in vivo release of luteinizing hormone as well as the in vitro hypothalamic release of gonadotropin-releasing hormone (GnRH). In order to study the influence of NO on GnRH mRNA expression, two inhibitors of NO synthase (NOS) NG-monomethyl-l-arginine (NMMA) and HP-228, were microinjected into the left lateral ventricle of sham-operated and castrated male rats 4 h before sacrifice. Since the dopaminergic system can positively influence GnRH gene expression, we have also measured in the same animals tyrosine hydroxylase (TH) mRNA in tuberoinfundibular dopamine (TIDA) neurons. GnRH and TH mRNA levels were measured at the cellular level by quantitative in situ hybridization. The injection of HP-228 or NMMA induced a similar decrease (-19.5%) in GnRH mRNA. In castrated animals, the hybridization signal was 88% higher than that observed in sham-operated animals. Both HP-228 and NMMA produced in castrated animals a 39% decrease in GnRH mRNA. In contrast the injection of NOS inhibitors resulted in an increase in the amount of TH mRNA in TIDA neurons. The stimulating effect was more striking in HP-228-treated (+60%) than in NMMA-treated (+32%) animals. Castration did not induce any changes in the number of silver grains overlying TIDA neurons, while the administration of either HP-228 or NMMA induced a 43% increase in castrated animals. These results together with previous ones on GnRH release in vitro suggest that NO exerts a positive influence not only on the secretion but also on the biosynthesis of GnRH. Since NO appears to play a role in the negative regulation of dopamine, it is likely that the increase in GnRH mRNA expression is not mediated by the TIDA system.
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PMID:Role of nitric oxide in the regulation of gonadotropin-releasing hormone and tyrosine hydroxylase gene expression in the male rat brain. 959 26

We examined the effect of intracerebroventricular (i.c.v.) administration of mu-opioid agonist, morphine, and its antagonist naloxone followed by morphine on the activities of monoamine-metabolizing enzymes, namely tyrosine hydroxylase (TH) and monoamine oxidase (MAO) along with adenosinetriphosphatase (Na+, K+ -ATPase), the enzyme responsible for the maintenance of ionic gradients across the membrane, in seven discrete regions of brain from estrogen- and progesterone-primed ovariectomized rats. TH activity decreased after morphine treatment in some areas such as the median eminence-arcuate region (ME-ARC), the amygdala, and the thalamus, showing statistically significant change. MAO activity increased in all the areas studied, but more appreciable change was observed in medial preoptic area (mPOA), the ME-ARC region, and the cortex. Pronounced increase in Na+, K+ -ATPase enzyme activity was observed after the drug treatment. Naloxone given prior to morphine injection resulted in recovery of the enzyme activities in most of the areas studied. Our study may provide insights into the precise opioidergic modulation of gonadotropin releasing hormone (GnRH) release mechanisms through the involvement of monoaminergic system, elucidating the basis of various neuronal dysfunctions and their management in opioid addicts.
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PMID:Role of opioidergic and monoaminergic neurotransmission in the GnRH release mechanism of EBP-primed OVX rats. 976 93

Gonadal steroids exert a powerful regulatory influence upon the functioning of gonadotropin-releasing hormone (GnRH) neurons despite the apparent absence of gonadal steroid receptors in these cells. By using retrograde-tracing techniques combined with dual-labeling immunocytochemistry, we show here that distinct populations of estrogen receptor alpha (ERalpha)-containing neurons located in the hypothalamus and caudal brainstem project to the vicinity of the GnRH perikarya located in the rostral preoptic area (rPOA). The strongest estrogen-receptive afferent projection to this area originated from neurons located in the anteroventral periventricular and medial preoptic nuclei of the preoptic area. Approximately 50% of arcuate nucleus neurons projecting to the rPOA were demonstrated to synthesize either neuropeptide Y or beta-endorphin, but little evidence was found for ERalpha immunoreactivity in either of these specific subpopulations. Over 80% of all tyrosine hydroxylase-expressing neurons in the arcuate nucleus expressed ERalpha, but none projected to the rPOA. In the caudal brainstem, the A1 and A2 norepinephrine neurons comprised nearly all of the retrogradely labeled neurons. However, only the A2 afferents expressed ERalpha immunoreactivity, whereas the A1 afferents coexpressed neuropeptide Y. These observations, combined with the anterograde labeling data of others, provide neuroanatomical evidence for the existence of specific estrogen-receptive neuronal cell populations that project to the rPOA and may be involved in the estrogen-dependent transsynaptic regulation of GnRH neurons in the rat.
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PMID:Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. 1040 58


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