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)

Estrogen effects on tyrosine hydroxylase (TH), monoamine oxidase types A and B (MAO), and dopamine (DA) in microdissected regions of the hypothalamus, preoptic area and substantia nigra (SNR) of the female rat brain were investigated. Ovariectomized (OVX) young adult female rats were implanted with single silastic capsules containing 100% estradiol valerate (EV). Control rats received empty silastic capsules. Two weeks following capsule insertion, EV decreased TH activity and DA concentration in the arcuate nucleus (AN) while no significant changes in TH activity or DA concentration were observed in the SNR, ventromedial nucleus (VMN), suprachiasmatic nucleus, paraventricular nucleus, medial preoptic nucleus, or the periventricular preoptic nucleus. Although estrogen suppressed TH and DA in the AN, 2 weeks following removal of the estrogen containing capsules, TH activity and DA concentration were restored to control (OVX) levels. Suppression of MAO activity occurred in both the AN and the VMN of rats implanted with EV capsules and returned to OVX levels following the removal of the estradiol load. These results revealed that estrogen effects on TH and MAO activities and DA concentration in the midbrain are region specific and reversible; and that among the dopaminergic systems studied, estrogen effects on TH and DA are confined to the tuberoinfundibular dopaminergic system (TIDAS). Furthermore, these results support our hypothesis that estrogen is a key regulator of DA function in the TIDAS via effects on TH. The importance of these findings to the control of gonadotropin secretion and reproductive cyclicity is discussed.
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PMID:Estrogen effects on the tuberoinfundibular dopaminergic system in the female rat brain. 196 60

Previous studies indicate that the major pelvic ganglion (PG) is dependent on testosterone for normal development. Tyrosine hydroxylase (T-OH), DOPA decarboxylase, and choline acetyltransferase (CAT) activities are significantly reduced by postnatal castration on day 10-11, while testosterone replacement therapy reversed all developmental enzyme activity deficits (Melvin and Hamill, 1987). In the present studies castration on the day of birth combined with various testosterone-replacement paradigms produced effects demonstrating that the PG is sensitive to testosterone dosage and time of administration during early postnatal development. Gonadal hormone replacement experiments show that the androgens testosterone and dihydrotestosterone were effective in restoring T-OH and CAT activity deficits produced by neonatal castration. Estrogen therapy reversed the deficits in CAT activity, but was ineffective in reversing the alterations in T-OH activity. Treatment of pregnant dams with the anti-androgen flutamide altered the ontogeny of T-OH and CAT activities in pups despite replacement therapy on the day of birth. Thus, androgen-critical periods exist prenatally as well as postnatally. These studies suggest that the organization of PG development is critically dependent on both the time of exposure and dose of testosterone. Prenatal and postnatal critical periods appear to exist. In addition, the lack of an effect of estradiol on tyrosine hydroxylase activity suggests that androgens are specifically responsible for organizing the noradrenergic development of the PG.
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PMID:Androgen-specific critical periods for the organization of the major pelvic ganglion. 291 85

The presence of enzymatic activity (tyrosine hydroxylase, dopa-decarboxylase, dopamine-beta-hydroxylase, monoamine oxydase and catechol-O-methyl transferase), as well as dopamine (DA) content and DA synthesis from tyrosine and dopa, were investigated in intact rats partes distales and in grafts (both estrogenized and nonestrogenized). Counts of prolactin cells showed the following regression in the number of these cells: estrogenized grafts greater than nonestrogenized grafts greater than intrasellar intact glands. Tyrosine hydroxylase activity was not found in intact glands, but this enzyme was detected in the two types of grafts. An approximate correlation could be established between the number of prolactin cells and the diverse enzyme activities. Dopamine was not synthesized from tyrosine in intact glands, but it occurred in the transplants. However, when dopa was used, both intact and grafted glands produced dopamine. Estrogen administration decreased dopamine content in all the glands investigated. The significance of these results in relation to the physiology of the pars distalis is discussed.
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PMID:Catecholamine metabolizing enzymes and synthesis of dopamine in normal and grafted pituitary partes distales. 664 50

In order to elucidate cellular events responsible for sex differentiation of the nigro-striatal system, we studied the influence of estrogen on the expression of tyrosine hydroxylase (TH) in sex-specific dissociated cell cultures of embryonic day 14 rat mesencephalon. Cultures were raised in the absence or presence of 17 beta-estradiol (10(-12) M) and hybridized with a [35S]oligonucleotide specific to TH. Cultured cells and tissues were probed for estrogen receptor (ER) transcripts by hemi-nested PCR. More TH mRNA containing cells were present in control cultures from female than from male donors. Estrogen treatment resulted in an up-regulation of TH expression in male cells only and induced a reversal of the sex difference in TH mRNA levels present in early control cultures. ER message was detectable in hypothalamic and uterine tissues but not in mesencephalic tissue or cultured cells. Estrogen exposure failed to induce ER expression in cultured mesencephalic cells. It is concluded that there are sex differences in TH mRNA expression of developing midbrain dopaminergic neurons which are independent of the steroid environment. Estrogen can up-regulate TH mRNA in a sex-specific fashion by modulating signal transduction mechanisms other than the classical nuclear receptor pathway.
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PMID:Effects of sex and estrogen on tyrosine hydroxylase mRNA in cultured embryonic rat mesencephalon. 877 57

Gonadal hormones influence brain functions, including motor and motivational behaviors, transmitter release, and receptor binding in midbrain dopamine systems. Much of this influence suggests genomic hormone action. To identify which midbrain cells may be targets of genomic influence, double label immunocytochemistry was used to map intracellular estrogen and androgen receptors and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA), substantia nigra (SN), and retrorubral fields (RRF) in intact, adult rats. The distribution of estrogen and androgen receptor immunoreactivity was highly selective, similar in males and females, and largely nonoverlapping. Estrogen receptors were present within subpopulations of cells in the ventrolateral paranigral VTA and rostrolateral RRF; of these, only a few cells in the RRF were immunoreactive for TH. Cells immunoreactive for androgen receptors were numerous in the paranigral and parabrachial VTA, SN pars lateralis and dorsomedial pars compacta, and lateral RRF. Nearly every androgen receptor-bearing cell in the VTA and SN pars compacta, roughly half in the SN pars lateralis, and about one-third in the RRF were TH immunopositive. The localization of estrogen receptors approximates the distribution of subsets of cells labeled following neostriatal injections, whereas androgen receptors tend to occupy regions labeled by injections in cortical or limbic targets. These receptor-specific alignments with origins of nigrostriatal, mesolimbic, and mesocortical projections are consistent with identified estrogen influence over motor behaviors and androgen involvement in motivational functions and may hold clues for understanding hormone action in these and other functions and dysfunctions of midbrain dopamine systems.
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PMID:Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area, substantia nigra, and retrorubral fields in the rat. 905 Jul 88

Recent studies have shown that ovariectomy reduces, and subsequent hormone replacement restores the density of axons immunoreactive for tyrosine hydroxylase in the dorsolateral prefrontal cortex of adult female rhesus monkeys. The present study indicates that three additional extrathalamic frontal lobe afferents are also sensitive to changes in the ovarian hormone environment. Specifically, the combination of hormone manipulation with qualitative and quantitative analysis of immunocytochemistry for dopamine beta-hydroxylase, choline acetyltransferase, and serotonin in the primate prefrontal cortex revealed quantitative responses in both cholinergic and monoaminergic axons to changing ovarian hormone levels. However, whereas ovariectomy produced a modest net decrease in the density of fibers immunoreactive for choline acetyltransferase, this same treatment markedly increased the density of axons immunoreactive for dopamine beta-hydroxylase and for serotonin. Further, the effects of ovariectomy on these afferent systems were differentially attenuated by estrogen verses estrogen plus progesterone hormone replacement. Estrogen was as effective as estrogen plus progesterone in stimulating normal prefrontal immunoreactivity for choline acetyltransferase and dopamine beta-hydroxylase. The dual replacement of estrogen plus progesterone, however, was a much more potent influence than estrogen alone for serotonin immunoreactivity. Thus, ovarian hormones appear to provide stimulation that differentially affects each of four chemically identified extrathalamic prefrontal afferent systems examined to date, and may have roles in maintaining the normal balance and functional interactions between these neurotransmitter systems.
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PMID:Ovarian hormones differentially influence immunoreactivity for dopamine beta- hydroxylase, choline acetyltransferase, and serotonin in the dorsolateral prefrontal cortex of adult rhesus monkeys. 1037 29

Previously, we demonstrated that exposure to morphine during gestation increases hypothalamic norepinephrine (NE) content and turnover rate in adult male rats and decreases these measures in adult females. To investigate the basis of these alterations, the present study examined the effects of prenatal exposure to morphine on tyrosine hydroxylase immunoreactivity (TH-IR) in the brains of adult male and female progeny. In male rats, prenatal morphine exposure significantly increased the density of TH-IR in cells and fibers in the caudal paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus (LC), but had no effects in the lateral hypothalamus (LH). In female rats that were ovariectomized (OVX), prenatal morphine exposure significantly decreased the density of TH-IR in cells and fibers in the LC. Interestingly, an injection of estrogen in OVX control females reduced the mean optical density of TH-IR in the LC, but it was ineffective in drug-exposed females in the same brain region. Estrogen injections also reduced the mean optical density of TH-IR in the LH but not in the PVN of females, regardless of prenatal drug exposure. Thus, the present study suggests that prenatal morphine exposure induces long-term, sex-specific alterations in TH-IR in the PVN and LC of adult progeny.
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PMID:Prenatal morphine exposure differentially alters TH-immunoreactivity in the stress-sensitive brain circuitry of adult male and female rats. 1071 19

Estrogen-dependent enhancement of glucoprivic-induced luteinizing hormone (LH) suppression is hypothesized to be due to increased estrogen receptor alpha (ERalpha)-immunoreactive (ir) cells in specific brain nuclei in a manner similar to fasting. ERalpha expression in various brain areas was determined in ovariectomized rats after systemic 2-deoxy-D-glucose (2DG)-induced glucoprivation. Expression of ERalpha in catecholaminergic neurons in the lower brainstem was also examined. ERalpha-ir cells increased in hypothalamic paraventricular and periventricular nuclei, and A1 and A2 regions of the brainstem 1 h after 2DG injection. The percentage of ERalpha in the tyrosine hydroxylase (TH)- and dopamine-beta-hydroxylase (DBH)-ir neurons was higher in A1 and A2 regions of 2DG-treated rats, but the number of TH- and DBH-ir cells did not change. Thus, 2DG induces ERalpha expression in specific brain nuclei and expression of ERalpha in catecholaminergic neurons of the brainstem indicates a role for estrogen in activating those neurons projecting to the hypothalamic paraventricular nucleus to suppress LH secretion during glucoprivation.
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PMID:Glucoprivation increases estrogen receptor alpha immunoreactivity in the brain catecholaminergic neurons in ovariectomized rats. 1116 50

Although estrogen is recognized increasingly as having an important role in modulating extrahypothalamic brain function, the mechanisms through which this occur are not well established. The norepinephrine (NE) neurons of the locus coeruleus provide an important neuromodulatory influence upon multiple neural networks throughout the brain and estrogen has been implicated in their regulation. Using a tyrosine hydroxylase (TH) promoter-LacZ transgenic mouse model, which enables rates of TH gene transcription to be examined in vivo, we have examined here whether estrogen regulates expression of the TH gene in the locus coeruleus of males and females. Optical area measurements of Xgal reaction product in the locus coeruleus revealed that gonadectomy exerted opposite effects on TH gene transcription in males and females; transgene expression was increased in males (P<0.01) but reduced in females (P<0.05). Estrogen reversed these effects in both sexes by suppressing gene expression in males (P<0.05) but elevating it in the female (P<0.05). These studies reveal a marked and unexpected sex difference in the regulation of TH gene activity in the mouse. While estrogen in the male, synthesized from circulating testosterone, suppresses TH gene transcription, estrogen in the female enhances TH promoter activity. The present results indicate that estrogen may exert very different sex-dependent effects upon the biosynthesis of NE within the locus coeruleus.
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PMID:Sex differences in the regulation of tyrosine hydroxylase gene transcription by estrogen in the locus coeruleus of TH9-LacZ transgenic mice. 1222 77

Estrogen plays an important role during differentiation of midbrain dopaminergic neurons. This is indicated by the presence of estrogen receptors and the transient expression of the estrogen-forming enzyme aromatase within the dopaminergic cell groups. We have previously shown that estrogen regulates the plasticity of dopamine cells through the stimulation of neurite growth/arborization. In this study, we have analyzed the capability of estrogen to influence the activity of developing mouse dopamine neurons. The expression of tyrosine hydroxylase (TH) was assessed by competitive RT-PCR and Western blotting. The developmental expression of TH in the ventral midbrain was studied from embryonic day 15 until postnatal day 15 and revealed highest TH levels early postnatally. This profile coincides with the transient aromatase expression in this brain area. Using cultured midbrain cells, we found that estrogen increased TH mRNA/protein levels. The application of the estrogen receptor antagonist ICI 182,780 resulted in a complete inhibition of estrogen effects. To verify these data in vivo, fetuses were exposed in utero from E15 until birth to the aromatase inhibitor CGS 16949A or to CGS supplemented with estrogen. CGS caused a robust reduction in TH mRNA/protein levels in the midbrain, which could be restored by estrogen substitution. Taken together, our data strongly suggest that estrogen controls dopamine synthesis in the developing nigrostriatal dopaminergic system and support the concept that estrogen is implicated in the regulation of ontogenetic steps but also in the function of midbrain dopamine neurons.
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PMID:Estrogen regulates tyrosine hydroxylase expression in the neonate mouse midbrain. 1255 75


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