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 immediate-early gene c-fos (a nuclear transcription factor) has been viewed as a nuclear "third messenger" or cellular "master switch." Both in vitro and in vivo studies have suggested that the proenkephalin (Penk) and tyrosine hydroxylase (TH) genes are potential targets of this immediate-early gene. We investigated the relationships between the activation of the c-fos gene and the activation of the Penk and TH genes in both rat hippocampus and adrenal using a commonly used model, metrazole (MTZ)-induced convulsions. The administration of MTZ produced a sequential elevation in c-fos, preproenkephalin (PPenk), and TH mRNAs. One hour after MTZ administration, c-fos mRNA was increased about 10-fold in rat hippocampus and about 5-fold in rat adrenal, without a significant change in spinal cord levels. Immunocytochemistry revealed that Fos-like immunoreactivity was greatly increased in both hippocampus and adrenal medulla at 3 hr after MTZ administration. The levels of PPenk and TH mRNAs were significantly increased (5-fold and 3-fold, respectively) in the adrenal 6 hr after MTZ treatment. The effects of MTZ on c-fos, PPenk, and TH mRNAs were dose dependent in both adrenal and hippocampus. In the adrenal, both the basal levels and the MTZ induction of PPenk mRNA were significantly attenuated by hypophysectomy (hypox) and were partially reinstated by adrenocorticotropic hormone (ACTH) replacement. In contrast, the basal levels of c-fos and TH mRNAs were not altered in hypox rat adrenal. ACTH treatment completely blocked the MTZ induction of adrenal c-fos mRNA and the subsequent induction of Fos-like immunoreactivity, whereas MTZ increased PPenk and TH mRNAs nearly 3-fold. Thus, in hypox rats MTZ can increase adrenal c-fos and TH mRNA levels without a corresponding increase in PPenk mRNA, whereas in ACTH-treated rats PPenk and TH mRNA levels in adrenal can be increased by MTZ without a preceding increase in c-fos mRNA. The MTZ induction of c-fos appears neither sufficient nor always necessary for the subsequent MTZ induction of Penk and TH gene expression. We conclude that c-fos, Penk, and TH genes can be differentially regulated in the adrenal of hypox rats or animals treated with ACTH, although they are co-localized in the same medullary cells.
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PMID:Metrazole induces the sequential activation of c-fos, proenkephalin, and tyrosine hydroxylase gene expression in the rat adrenal gland: modulation by glucocorticoid and adrenocorticotropic hormone. 810 82

Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.
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PMID:Genetic linkage analysis of manic depression in Iceland. 810 81

The expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was studied in the striatum of C57B1/6 mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP), which are used as a rodent model of Parkinson's disease (PD). Two weeks after systemic administration of MPTP (2 x 40 mg/kg, s.c. 18h apart), the lesion of the substantia nigra (SN) could be visualised by loss of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91% decrease in striatal dopamine levels. The levels of PENK and PDYN mRNAs were not significantly changed in the striatum of the lesioned mice, as compared to non-treated controls. The induction of the immediate early gene c-fos by the dopamine D2 receptor antagonist haloperidol was not altered, while the selective D1 receptor agonist SKF 38393 failed to induce c-fos in the striatum of MPTP-treated mice. These results are in contrast to the data concerning rats with the 6-hydroxydopamine (6-OHDA) lesion of the SN, which serve as another rodent model of PD. In the striata of 6-OHDA-lesioned rats, PENK gene is upregulated, PDYN gene is down-regulated and the induction of c-fos gene by D2 receptor antagonists is abolished, whereas selective D1 receptor agonists induce c-fos gene, which does not occur in non-lesioned rats. We presume that the lack of influence of the MPTP lesion in mice on the striatal gene expression was mainly caused by insufficient dopamine depletion in the striatum, which could not be increased in this model. The importance of the changes observed in 6-OHDA-lesioned rats has been discussed in the context of the mouse and primate MPTP models of PD.
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PMID:The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the straitum of MPTP-treated mice. 852

The anteroventral periventricular nucleus (AVPV) is a nodal point in neural circuits regulating secretion of gonadotropin and contains sexually dimorphic populations of hormonally regulated dopamine-, dynorphin-, and enkephalin-containing neurons. Because the tyrosine hydroxylase (TH), prodynorphin (PDYN), and proenkephalin (PENK) genes contain cAMP response elements that control their expression in their promoters, we used histochemical methods to determine whether ovarian steroids alter expression of the cAMP response element-binding protein (CREB) in the AVPV. Because the ability of CREB to activate transcription depends on phosphorylation at Ser133, we also evaluated the effects of acute steroid treatment on levels of phosphorylated CREB (pCREB) in AVPV neurons by using an antibody that differentiates between CREB and pCREB. Treatment of ovariectomized rats with estradiol treatments caused a significant induction in the number of pCREB-immunoreactive nuclei within 30 min that was maintained for at least 4 hr, but did not alter CREB immunostaining in the AVPV. Pretreatment with the estrogen antagonist Nafoxidine blocked this induction. In contrast, acute administration of progesterone to estrogen-primed animals suppressed and then increased pCREB staining in the ASVPV at 30 and 60 min, respectively; no significant differences between experimental and control animals were apparent by 2 hr after progesterone treatment. Double-labeling experiments showed that pCREB was colocalized with PDYN, PENK, or TH mRNA in the AVPV, suggesting that pCREB may mediate the effect of steroid hormones on gene expression in these neurons.
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PMID:Hormonal regulation of CREB phosphorylation in the anteroventral periventricular nucleus. 862 33

Sympathetic ganglia are the major contributors to the stress-elicited rise in circulating norepinephrine, enkephalins, and neuropeptide Y. Here we examined the effect of immobilization stress and treatment with ACTH and glucocorticoids on messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), preproneuropeptide Y (pre-NPY), and proenkephalin in rat superior cervical ganglia (SCG) and in stellate ganglia. Our results show a severalfold increase in the relative abundance of TH and NPY mRNAs in response to a single immobilization. Repeated stress elevated expression of all the genes studied and increased TH immunoreactivity in both ganglia. The effect of stress was more pronounced in SCG. Prolonged cortisol administration failed to alter the mRNA levels of TH, DBH, and NPY in control animals but attenuated the response to stress. In contrast, TH and DBH mRNA levels in the SCG, but not in adrenal medulla, were elevated by ACTH administration, similar to the levels attained after immobilization. The results revealed that the regulation of gene expression in response to immobilization stress in sympathetic neurons differs from the regulation in adrenal medulla. The study implicates hormonal involvement in the stress-induced changes in TH, DBH, NPY, and proenkephalin gene expression in sympathetic ganglia.
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PMID:Immobilization stress elevates gene expression for catecholamine biosynthetic enzymes and some neuropeptides in rat sympathetic ganglia: effects of adrenocorticotropin and glucocorticoids. 894 Mar 89

Proenkephalin (Penk) gene expression is high in the adult hamster adrenal medulla and it is comparable to that found in both the hamster and rat striatum. In addition, Penk gene expression in the hamster adrenal medulla is more typical of adult mammalian adrenals than the rat. Since the nature of Penk gene expression in the developing hamster adrenal is not known, it was examined and compared to that found in the striatum were adult levels in the adrenal and striatum are similar. The results show that Penk gene expression progressively increases in the developing hamster adrenal to peak on postnatal day 4. There is then a small decline to adult levels by postnatal day 12 when the morphology of the developing adrenal resembles the adult. Functional splanchnic nerve activity, as assessed by the ability of reserpine to induce increases in adrenal tyrosine hydroxylase mRNA, is not present until after postnatal day 4. Therefore, early increases in Penk gene expression are independent of splanchnic nerve activity. Adrenal EC peptides resulting from the developmental increases in Penk gene expression appear to be unprocessed and proenkephalin-like. This is based on the very low levels of free enkephalin (met-enkephalin) detected in the adrenals from both newborn and adult hamsters (1-5% of total EC peptide levels). In the developing hamster striatum, Penk gene expression remains low and unchanged until postnatal day 4 and increases six-fold by adulthood. Free enkephalin (met-enkephalin) levels remain high (between 36 and 88% of total EC peptide levels) in the developing and adult hamster striatum. Therefore the results show early increases in adrenal Penk gene expression in the developing hamster that are independent of splanchnic nerve activity and adult Penk gene expression which is high and dependent on splanchnic nerve activity. This differs from what is observed in the frequently studied rat. However, developmental changes in the hamster striatum are similar to those in the rat.
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PMID:Changes in proenkephalin gene expression in the developing hamster. 926 96

We have demonstrated that there are differential changes in the levels of tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and proenkephalin A (Pro Enk A) mRNA in the fetal sheep adrenal during late gestation. Adrenal TH mRNA:18S rRNA ratios increased between gestational days 100 (0.98 +/- 0.13; n = 6) and 125 (1.40 +/- 0.15; n = 6) and then decreased, whereas adrenal PNMT mRNA:18S rRNA ratios increased regularly between gestational days 100 (0.08 +/- 0.01) and 146 (0.17 +/- 0.03). The ratio of adrenal Pro Enk A mRNA to 18S rRNA was higher at gestational day 125 (0.085 +/- 0.005) than at either 80-100 days (0.038 +/- 0.007) or 140-146 days of gestation (0.055 +/- 0.013). In 12 ewes, the growth and development of the placenta were restricted (placental restriction group) from conception. The ratio of adrenal PNMT mRNA to 18S rRNA was significantly reduced in the placental restriction group of fetal sheep (0.003 +/- 0.002) compared with controls (0.011 +/- 0.002), and there was a significant correlation between the ratio of adrenal PNMT mRNA to 18S rRNA and the mean arterial PO2 (r = 0.88, p < 0.0005). In contrast, TH mRNA and Pro Enk mRNA were unaffected by placental restriction. Adrenaline and noradrenaline syntheses are therefore differentially regulated in the adrenal during late gestation and in response to chronic intrauterine hypoxemia.
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PMID:Differential effects of increasing gestational age and placental restriction on tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and proenkephalin A mRNA levels in the fetal sheep adrenal. 964 89

This study examined the impact of a chronic physiological elevation of plasma cortisol levels on adrenal catecholamine synthetic enzyme and proenkephalin A mRNA expression in foetal sheep. Cortisol (2.5-3. 0 mg.5 ml-1.24 h-1, n=9) or saline (0.9% saline, n=6) was infused into foetal sheep for 7 days between 109 days and 116 days gestation. Foetal plasma cortisol concentrations were higher (P<0.0005) in the cortisol infused foetuses when compared with the saline infused group (43.07+/-4.13 nmol.l-1 vs 1.67+/-0.10 nmol.l-1). There were no differences, however, in the plasma ACTH levels between the two groups. Using Northern blot analysis, adrenal phenylethanolamine N-methyltransferase (PNMT) mRNA expression was found to be reduced (P<0.005) fivefold in the cortisol infused foetuses when compared with the controls, as was the relative area of the adrenal medulla which stained positively with anti-PNMT (28.1+/-2.5% vs 44.8+/-4.8%, P<0.007). No effect of cortisol infusion was observed on adrenal tyrosine hydroxylase mRNA and protein expression or proenkephalin A mRNA expression. We conclude that before birth, adrenaline synthesis may be suppressed by a novel direct, or indirect, inhibitory effect of glucocorticoids on PNMT mRNA expression.
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PMID:Glucocorticoids decrease phenylethanolamine N-methyltransferase mRNA expression in the immature foetal sheep adrenal. 1044 14

It has been recently suggested that the effects of cannabinoids on motor behavior might be different in rats with lesions of nigrostriatal dopaminergic neurons than in controls. In the present study, we examined the possible alteration in the status of cannabinoid CB1 receptors in the basal ganglia of rats with unilateral lesions of those neurons caused by 6-hydroxydopamine. We used two different experimental groups depending on the duration of the period of recovery after the lesion, and comparisons were done between the lesioned and nonlesioned sides at the level of the basal ganglia. Both groups of lesioned rats exhibited a similar marked reduction in tyrosine hydroxylase (TH)-mRNA levels, measured by in situ hybridization, in the substantia nigra of the lesioned side. In the same way, lesioned rats exhibited the characteristic rotational behavior after a single injection of apomorphine and the intensity of this rotation was stable at the two times analyzed after the lesion. Also as expected, lesioned rats exhibited an increase in proenkephalin mRNA levels in the caudate-putamen, whereas mRNA levels of substance P decreased, although differences between the two times of recovery analyzed were observed in this case. We did not find any significant changes in CB1 receptor binding, measured by [3H]WIN-55,212,2 autoradiography, or in the activation of signal transduction mechanisms, measured by WIN-55,212,2-stimulated [35S]GTPgammaS binding autoradiography, between the lesioned and nonlesioned sides at the level of the lateral caudate-putamen, globus pallidus and substantia nigra in both groups of lesioned rats. However, we found a significant increase in levels of CB1 receptor-mRNA transcripts, measured by in situ hybridization, in the lesioned side in both the lateral and medial caudate-putamen. This occurred 7-10 weeks after the lesion, but the increase was markedly waned after 17-18 weeks. In summary, the unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons originated a marked increase in CB1 receptor-mRNA levels in cell bodies of striatal efferent neurons, although accompanied by no changes in CB1 receptor binding and activation of signal transduction mechanisms. This supports a critical role for dopamine in the control of CB1 receptor gene expression. However, the magnitude of the effect significantly waned as a function of the duration of the period after lesion.
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PMID:Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudate-putamen. 1079 65

The effect of cycloheximide (CHX; 5 mg/kg) on proenkephalin (proENK) and tyrosine hydroxylase (TH) mRNA expression in rat central and peripheral nervous systems was studied. CHX increased proENK and TH mRNA levels in the adrenal gland, but not in hippocampus, striatum, midbrain, brainstem, pituitary, and hypothalamus. The pretreatment with actinomycin D (0.5 mg/kg) significantly decreased CHX-induced proENK and TH mRNA expression, suggesting that the CHX-dependent increase of these mRNA levels may be caused by the increase of transcriptional activity rather than RNA stabilization. To investigate the factors involved in CHX-induced proENK and TH mRNA expression, the effect of CHX on activator protein-1 (AP-1), cAMP response element (CRE) binding protein (CREB), and glucocorticoid response element (GRE) was tested. In AP-1, the basal expression of Fra-2 and c-Jun proteins and AP-1 DNA binding activity in the adrenal medulla was higher than other tissues tested, but CHX reduced these protein levels and AP-1 DNA binding activity. In CREB, CHX time dependently increased the level of phospho-CREB without altering total CRE level and CRE DNA binding activity. Furthermore, phospho-CREB actively participated in CRE DNA binding activity. In GRE, although CHX increased plasma and adrenal corticosterone level, RU486 (10 mg/kg) reduced CHX-induced proENK, but not TH, mRNA level in a partial manner. These results suggest that the basal expression of proENK and TH mRNA transcription in the adrenal gland seems to be tonically inhibited by de novo protein synthesis. In addition, CHX-dependent increase of proENK and TH mRNA expression in the adrenal medulla is well correlated with phospho-CREB level, but not AP-1. Finally, glucocorticoid seems to be involved at least partially in CHX-dependent proENK, but not TH, mRNA expression in the adrenal medulla.
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PMID:Cycloheximide increases proenkephalin and tyrosine hydroxylase gene expression in rat adrenal medulla. 1082 88


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