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)

The aims of this study were to characterize the ontogeny of catecholamines (CA) in the rat ovary, to determine the ability of the immature ovary to synthetize norepinephrine (NE) in vitro, and to correlate between ovarian CA and plasma pituitary hormones. Ovaries, spleen (as a control tissue not subjected to endocrine regulation), and trunk blood were collected at 5-day intervals between days 5 and 40. Ovarian NE concentration increased markedly between days 20 and 35 of life, whereas the major rise in splenic NE concentration occurred between days 10 and 15. Ovarian and splenic tissues from neonatal females were capable of de novo synthesis of NE from tritiated tyrosine without an appreciable accumulation of L-Dopa and dopamine. The rate of NE synthesis by ovarian tissue taken from 20-day-old rats was significantly lower than that from 30- and 40-day-old rats, whereas NE production by splenic tissue from 20-, 30-, and 40-day-old rats were similar. Plasma FSH concentration was significantly elevated between days 10 and 20, whereas the major rise in plasma LH and PRL occurred between days 25 and 40. The following conclusions were reached. The delayed elevation of ovarian NE, compared to splenic NE, is attributable to a decreased production of NE by the ovary on day 20 and may involve a suppression or a delay in development of the activity of a key CA biosynthetic enzyme such as tyrosine hydroxylase. Given the temporal relationship between plasma gonadotropins, in particular FSH, and changes in ovarian NE, it is postulated that ovarian CA during neonatal development are subjected to regulation by circulating pituitary hormones.
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PMID:Norepinephrine in the rat ovary: ontogeny and de novo synthesis. 643 92

We have earlier reported that dopamine (DA) activity in the preoptic anterior hypothalamic (POA-AH) region of castrated rats is inhibited by testosterone and accelerated by PRL. These results suggested that dopaminergic neurons may play an important role in male copulatory behavior, particularly in the attenuation of sex behavior reported to be associated with hyperprolactinemia. We have now examined the effects of severe hyperprolactinemia on the POA-AH DA activity in association with any modifications of copulatory behavior. Sexually experienced adult male rats were castrated and implanted sc with Silastic implants containing testosterone to maintain serum testosterone levels in the range found in intact rats. Hyperprolactinemia was induced by inoculation of minced MtTW15 PRL secreting pituitary tumor fragments. Copulatory behavior was assessed at weekly intervals in hyperprolactinemic and control rats. During the period of tumor growth serum PRL levels increased logarithmically. Whereas sexual activity continued to improve in control rats, there was a marked decrease in several important parameters of copulatory behavior in hyperprolactinemic rats. The most dramatic decrease occurred in the percentage of tumor-bearing rats ejaculating which decreased progressively to zero at 6 weeks after tumor inoculation. Ejaculation frequency decreased and ejaculation latency increased in tumor-bearing rats before the complete disappearance of ejaculatory behavior. The deficits in copulatory behavior of hyperprolactinemic rats were accompanied in parallel studies by significant depletions of DA concentrations in the POA-AH. Further, neuronal activity, as evidenced by the turnover rates measured by rate of loss of DA after tyrosine hydroxylase inhibition with alpha-methyl paratyrosine, was markedly augmented in the POA-AH of hyperprolactinemic rats as compared to control animals. These findings disclose a close association between the acceleration in POA-AH DA activity and the attenuation of copulatory behavior induced by hyperprolactinemia and suggest the probability of an underlying role of the POA-AH DA neurons in male sex behavior normally induced by testosterone.
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PMID:Effects on male sex behavior and preoptic dopamine neurons of hyperprolactinemia induced by MtTW15 pituitary tumors. 664 26

The lack of PRL synthesis in Ames dwarf mice coincides with a marked reduction in dopamine (DA) and in numbers of PRL-inhibiting tuberoinfundibular dopaminergic neurons in the hypothalamus (catecholaminergic area A12), as assessed by tyrosine hydroxylase (TH) immunoreactivity. This DA/TH deficit develops postnatally and can be prevented by PRL replacement initiated at 12 days of age. The present study tested whether a similar PRL treatment in adult dwarfs would reverse the A12 deficit, indicating that these neurons are quiescent due to absent PRL feedback stimulation, or would not reverse the deficit, suggesting that A12 neurons are either absent or refractory to PRL effect. At 60 days of age, Ames dwarf (df/df) mice received renal pituitary allografts from normal (DF/df) donors as a source of mouse PRL. Separate groups of dwarfs were treated sequentially with ovine PRL (50 micrograms/day, ip; 30 days) and vehicle (15 days) to assess whether the putative restorative effect of PRL regressed after hormone withdrawal. Brains were evaluated using DA histofluorescence and TH immunocytochemistry. Total numbers of TH-immunostained cells in A12 and medial zona incerta (area A13) regions were counted, and the intensity of TH immunostaining was assessed by computerized image analysis. The total A12 TH-positive cell number was reduced (P < 0.01) in all PRL-treated dwarfs (1826 +/- 58) compared with that in normal mice (3340 +/- 180), and was not different from that in untreated dwarfs (1953 +/- 304) regardless of the PRL regimen. However, A12 perikarya in all PRL-treated dwarfs showed qualitatively increased histofluorescence and quantitatively increased TH immunostaining (P < 0.01) intensity compared with that in untreated dwarfs, an effect that regressed after ovine PRL withdrawal. Neither cell number nor staining intensity differed by gender. There were no significant differences in A13 cell numbers or staining intensity according to phenotype or PRL treatment. The present results indicate that the tuberoinfundibular dopaminergic neuronal population in adult Ames dwarf mice is permanently reduced, although extant A12 cells in dwarfs are responsive to either homologous or heterologous PRL feedback. Together with the previously reported effect of PRL treatment in neonatal dwarfs, the reduction appears to be the result of absent PRL stimulation during development.
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PMID:Prolactin replacement in adult dwarf mice does not reverse the deficit in tuberoinfundibular dopaminergic neuron number. 754 42

Exposure of golden hamsters to a short photoperiod (< 12.5 h light/day) leads to suppression of gonadal function secondary to reduced gonadotropin and PRL secretion. PRL secretion is decreased despite a reduction of tuberoinfundibular dopaminergic activity. In the present study, the ability of photoperiod to affect tuberohypophyseal dopamine (DA) turnover was evaluated in long day (LD; 16 h of light, 8 h of darkness) and short day (SD; 8 h of light, 16 h of darkness) male hamsters. Exposure to SD led to decreases in testicular weight within 10 weeks and decreases in plasma PRL levels within 1 week. DA turnover in the neurointermediate lobe of the pituitary, as estimated by measuring the depletion of DA 60 min after tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine (250 mg/kg), was significantly elevated 1 and 4 weeks after transfer to SD, but returned by 10 weeks to the levels seen in LD animals. After 14 days of SD exposure an enhanced lactotroph sensitivity to DA was demonstrated and may also have contributed to suppression of PRL levels. Similarly to the findings of previous studies, DA turnover in the median eminence was depressed in animals housed in SD. The DA content of the anterior pituitary was not significantly affected by photoperiod. The data from this study suggest that decreases in PRL secretion associated with the transfer of hamsters from LD to SD conditions are at least in part caused by an increase in DA turnover by neurohypophyseal neurons. However, the involvement of other PRL-inhibiting or -stimulating factors in mediating the effects of photoperiod on PRL secretion cannot be ruled out.
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PMID:Photoperiod effects on neurohypophyseal and tuberoinfundibular dopamine metabolism in the male hamster. 778 25

PRL release in primates can be stimulated by progesterone (P) after estrogen (E) priming. Hypothalamic dopaminergic neurons are a primary inhibitory system of PRL secretion, which differentially express progestin receptors (PR) in a cell-specific manner. Thus, these neurons may be an important target of P for increasing PRL. To further this hypothesis, two studies were performed. First, verification of the subpopulations of dopaminergic neurons that express PR was obtained with a combination of immunocytochemistry for PR and in situ hybridization for tyrosine hydroxylase (TH). Second, the effects of E and E plus P on the expression of TH messenger RNA (mRNA) were examined with in situ hybridization and image analysis in five different subpopulations of dopaminergic neurons. In the first study, dual labeled neurons were found rostrally around the ventral portion of the third ventricle and in more caudal periventricular areas, including the dorsal arcuate nucleus. Little or no PR were observed in TH-positive neurons located in the lateral chiasmatic area, paraventricular nucleus, ventral arcuate nucleus, or the substantia nigra. These results are consistent with our previous observations using double immunocytochemistry. In the second study, there was no significant effect of E or E plus P on single cell levels of TH mRNA in dopaminergic neurons of the subventricular area, periventricular area, or paraventricular nucleus. However, E plus P treatment produced a significant decrease in TH mRNA in the ventral arcuate dopaminergic neurons. There was no effect of E or E plus P in the dorsal arcuate dopaminergic neurons. In conclusion, E plus P decreases the expression of TH mRNA in the ventral arcuate dopaminergic neurons, a subpopulation that rarely expresses PR. The decrease in TH mRNA in the ventral arcuate dopaminergic neurons after E and P treatment is consistent with a role for this subpopulation of tuberoinfundibular neurons in P-induced PRL secretion.
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PMID:Steroid regulation of tyrosine hydroxylase messenger ribonucleic acid in dopaminergic subpopulations of monkey hypothalamus. 789 92

Labelling patterns of immunoreactive prolactin (IR-PRL)-containing and tyrosine hydroxylase (TH)-containing nerve terminals of the median eminence (ME) were compared in young adult (aged 3 months) and old (aged 24 months) male Wistar rats. In the young rats, IR-PRL- and TH-immunostained fibres extended throughout the external most layer of the ME. In the old rats, a significant decrease in the intensity of labelling of IR-PRL terminals was observed in this layer, with a slight reduction in the extent of labelling. As far as TH terminals were concerned, no difference could be detected between young and old animals.
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PMID:Evidence for an age-dependent decrease in the immunoreactive prolactin-containing terminals of the median eminence of male rats. 790 27

This study examined the intracellular mechanisms for the regulation of tyrosine hydroxylase in the tuberoinfundibular dopaminergic neurons of cycling female rats. It also evaluated the hormonal influences that contribute to the control of this enzyme on proestrus. Tyrosine hydroxylase messenger RNA (mRNA) levels in the arcuate nucleus of the hypothalamus were assessed by in situ hybridization. Tyrosine hydroxylase activity in the stalk-median eminence was determined from the in vitro or in vivo rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine or m-hydroxybenzylhydrazine, respectively. Tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation were similar on diestrous day 2 and proestrous mornings, but were reduced by 50% on estrus. Although circulating PRL concentrations were similar on the morning of each day of the estrous cycle, a broad preovulatory PRL surge was observed on the afternoon of proestrus. In vitro DOPA accumulation was similar at 1000 h before the PRL surge and at 1330 h during the peak phase of the PRL surge, but was reduced during the plateau phase of the PRL surge (1700 and 2200 h) coincident with the preovulatory progesterone rise and remained low on estrus. However, in vivo DOPA accumulation was transiently decreased only at 1700 h on proestrus. Tyrosine hydroxylase mRNA levels were similar at 1000, 1330, and 1700 h on proestrus, were reduced by 50% at 2200 h on proestrus subsequent to the decrease in enzyme activity, and remained low on the morning of estrus. Okadaic acid, a protein phosphatase-1 and -2A inhibitor, induced a similar increase in tyrosine hydroxylase activity in vitro at 1330 and 2200 h on proestrus and at 1100 h on estrus, indicating that tyrosine hydroxylase was capable of being activated in spite of decreased mRNA levels. Ovariectomy between 1100-1200 h on proestrus prevented the decrease in tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation at 2200 h. The effects of ovariectomy were completely reversed by progesterone, whereas estradiol had no effect. Circulating PRL levels at 2200 h were suppressed to basal levels after ovariectomy, but were increased by progesterone treatment at 1530 h to levels similar to those in the plateau phase of the PRL surge in control rats. Administration of the progesterone antagonist RU486 at 1200 h on proestrus did not alter tyrosine hydroxylase activity, tyrosine hydroxylase mRNA levels, or circulating PRL concentrations at 2200 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Progesterone suppresses tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nucleus on proestrus. 791 84

We previously reported that a factor(s) from rat choriocarcinoma (Rcho-1) cells suppresses circulating PRL levels and increases tyrosine hydroxylase activity in tuberoinfundibular dopaminergic neurons in vivo. The purposes of this study were to determine whether this factor(s) increases tyrosine hydroxylase activity in fetal hypothalamic cells in vitro and to evaluate its chemical nature. The Rcho-1 cells are of placental origin and have the capacity to differentiate into giant cells and produce members of the placental PRL family. MMQ cells, a pituitary cell line that secretes PRL, and HRP-1, a placental cell line that does not produce any known members of the PRL family, were used as control cells. Tyrosine hydroxylase activity was assessed by incubation of hypothalamic cells for 1 h with 100 microM brocresine, an inhibitor of aromatic L-amino acid decarboxylase. Tyrosine hydroxylase activity was increased in a density-dependent manner when Rcho-1, but not HRP-1 or MMQ, cells were cocultured with hypothalamic cells for 24 h. Control and Rcho-1-stimulated tyrosine hydroxylase activities were markedly reduced with 1 mM alpha-methyl-p-tyrosine, a specific inhibitor of tyrosine hydroxylase. Tyrosine hydroxylase activity was not altered when hypothalamic cells were incubated for 24 h with rat PRL or recombinant rat placental lactogen-I, whereas a 24-h stimulation with 100,000 Rcho-1 cells and a 1-h stimulation with 5 mM (Bu)2cAMP increased tyrosine hydroxylase activity 3.7- and 3-fold, respectively. The magnitudes of the increase in tyrosine hydroxylase activity were similar when hypothalamic cells were cocultured with Rcho-1 cells for 1 and 24 h. Acetic acid extracts of Rcho-1, but not HRP-1 or MMQ, cells increased tyrosine hydroxylase activity within 1 h in a concentration-dependent manner. The 3-fold increase in tyrosine hydroxylase activity observed with 500,000 Rcho-1 cell equivalents was markedly reduced with 1 mM alpha-methyl-p-tyrosine. The mol wt range of the tyrosine hydroxylase-activating factor(s) (THAF) was estimated using ultrafiltration membranes. The majority of activity was found in the eluate from a 1,000 mol wt cut-off membrane. THAF activity in Rcho-1 cell extracts was decreased by preincubation with pronase, a nonspecific proteolytic enzyme, suggesting that the factor(s) is a peptide. THAF was resistant to inactivation by trypsin or chymotrypsin pretreatment. However, both enzymes destroyed the ability of pituitary adenylate cyclase-activating peptide, either alone or with Rcho-1 cell extracts, to increase tyrosine hydroxylase activity. Oxidation of Rcho-1 cell extracts with performic acid abolished THAF activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A factor(s) from a trophoblast cell line increases tyrosine hydroxylase activity in fetal hypothalamic cell cultures. 810 May 18

Light and electron microscopic triple immunostaining was performed on coronal vibratome sections prepared from the hypothalamus of ovariectomized (OVX) and OVX plus estrogen-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for progesterone receptors (PRs) and neuropeptide-Y (NPY) was visualized by a dark blue to black nickel diaminobenzidine reaction, while the tyrosine hydroxylase-containing perikarya were labeled with a light brown diaminobenzidine reaction. In the OVX plus estrogen-treated material, 30% of the tyrosine hydroxylase-immunoreactive neurons contained PR-immunopositive nuclei. The majority of these cells were found in the central portion of the periventricular area, and a few could be observed in the anterior hypothalamus and the arcuate and dorsomedial hypothalamic nuclei. These tyrosine hydroxylase-immunoreactive PR-containing cells were surrounded with NPY-immunoreactive axon terminals. A correlated electron microscopic analysis of the same sections revealed synaptic contacts between these NPY-immunoreactive boutons and the PR-containing tyrosine hydroxylase-immunoreactive neurons. In contrast, in the OVX animals, no PR-containing tyrosine hydroxylase-immunoreactive neurons could be detected. In these monkeys, the frequency of synaptic contacts between the NPY-immunoreactive axon terminals and tyrosine hydroxylase-immunopositive cells was similar to that in the OVX plus estrogen-treated monkeys. These observations indicate that in a population of hypothalamic dopamine cells, the presence of nuclear PRs is estrogen dependent, show that these cells are innervated by NPY axons, and suggest that these estrogen-induced PR-containing dopamine neurons are involved in mediation of the effect of NPY on hypophyseal hormone secretion, including ovarian steroid hormone-dependent LH and PRL release.
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PMID:Neuropeptide-Y innervation of estrogen-induced progesterone receptor-containing dopamine cells in the monkey hypothalamus: a triple labeling light and electron microscopic study. 810 May 20

Suckling-induced PRL secretion is regulated in part by a reduction in tuberoinfundibular dopamine (TIDA) neuronal activity. We have examined the effects of suckling on TIDA activity in the arcuate nucleus by measuring changes in gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. TH gene expression was assessed by performing in situ hybridization, using a 35S-labeled antisense riboprobe for quantitating TH mRNA and analyzing grain density with the aid of an Optimas Bioscan image analysis system. Lactating rats suckled by eight pups were studied on postpartum day 10, and diestrous day 1 rats were used as controls. The results showed that lactation suppressed TH mRNA content throughout the arcuate nucleus to about 10% of diestrous levels. The dramatic reduction in TH mRNA during lactation was specific to the arcuate nucleus, as TH mRNA levels in the zona incerta were similar during lactation and diestrus. The suckling stimulus was the primary signal responsible for the suppression of TH mRNA in the arcuate nucleus, as removal of the pups for 6 h restored TH mRNA content to diestrous levels. By 24 h after pup removal, TH mRNA had reached almost twice diestrous levels. In view of the dramatic reduction in TH mRNA levels during lactation, we examined whether TH protein in the arcuate nucleus was similarly diminished. TH protein was detected by immunocytochemistry using a monoclonal antibody to TH. Qualitatively, TH staining was heavier in cell bodies, nerve fibers, and median eminence during diestrus. There was a small, but significant, decrease in TH-positive cell numbers during lactation (14% reduction) compared to those on diestrus. These data provide clear evidence that TH expression is suppressed during lactation, as evidenced by the decrease in TH mRNA and TH protein. The reduction in TH expression most likely contributes to the decrease in dopaminergic tone during lactation.
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PMID:Suppressed tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic system during lactation. 810 77


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