Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the relationships between the effects of glucocorticoids on rat pancreatic acinar AR42J cell polyamine levels and cellular growth and differentiation. Glucocorticoids inhibit the growth of AR42J cells. Glucocorticoids either stimulate or inhibit the formation of polyamines in a variety of cell types. Cells require polyamines for normal growth. Therefore, we tested the hypothesis that polyamines mediate the effects of glucocorticoids on AR42J cells. First, to confirm that AR42J cells required polyamines for growth we examined the effects of inhibiting ornithine decarboxylase (ODC). ODC is the most important and generally rate-limiting enzyme in the synthesis of the polyamines. As expected, the ODC inhibitor difluoromethylornithine (DFMO) inhibited AR42J cell DNA synthesis, and the addition of exogenous putrescine reversed this effect. The levels of growth inhibition by glucocorticoids and DFMO treatment were similar. Second, we examined the effects of glucocorticoids on ODC. Surprisingly, glucocorticoids increased levels of AR42J cell ODC mRNA, ODC activity, and putrescine. Glucocorticoids increased these parameters over a similar time-course as they decreased DNA synthesis. Analog specificity studies indicated that a glucocorticoid receptor mediated both the growth inhibitory and ODC stimulatory effects. Dose-response studies indicated, however, that growth inhibition was more sensitive to dexamethasone (DEX) than were ODC levels. Therefore, polyamines do not account for the effects of glucocorticoids on AR42J cell growth. In these cells, glucocorticoids have opposite and independent effects on ODC and growth.
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PMID:Glucocorticoids have opposite effects on ornithine decarboxylase and cell growth in pancreatic acinar AR42J cells. 134 62

The hormonal aspect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is discussed in relation to its carcinogenic potency for the gastric epithelium. The action of MNNG, as assessed in terms of a) the affinities for both the glucocorticoid receptor and androgen receptor of mouse, b) the effects on the turnover of hydrocortisone and dihydrotestosterone in the glandular stomach of mouse, c) the induction of ornithine decarboxylase in the same tissue, and d) the interfering effect on the hydrocortisone - linked acceleration of water turnover at the whole body level of a mouse, points to the steroid-mimetic nature of the carcinogen. It is suggested that MNNG may behave like an androgen antagonist on the one hand, and like a chimera between glucocorticoid agonist and glycocorticoid antagonist on the other hand. The proposition that a chemical carcinogen may have an interplay with the steroid and thyroid hormone receptor superfamily in the induction of malignant transformation is reviewed in the light of recent progress of steroid receptor biology.
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PMID:Is N-methyl-N'-nitro-N-nitrosoguanidine a hormonal carcinogen? (Review). 164 37

The effects of dexamethasone on ornithine decarboxylase gene expression were examined in rat pancreatic AR42J cells. Dexamethasone increased ornithine decarboxylase activity and messenger RNA (mRNA) concentrations in a time-dependent manner, with a maximal effect at 12 hours (207% +/- 63% and 327% +/- 34% of control, respectively; n = 5). Ornithine decarboxylase mRNA levels returned to control values at 48 hours, whereas ornithine decarboxylase activity was decreased to 41% +/- 8% of control (n = 3). Dexamethasone induction of ornithine decarboxylase mRNA was dose dependent, with half-maximal effects at 10(-8) mol/L (210% +/- 20% of control; n = 4) and maximal effects at 10(-7) mol/L (327% +/- 26% of control; n = 4). The glucocorticoid antagonist RU 38486 blocked the dexamethasone effects in a dose-dependent manner, with maximal effects occurring at 10(-7) mol/L (120% +/- 18% of control; n = 3). When protein synthesis was blocked by addition of cycloheximide, ornithine decarboxylase mRNA levels remained unchanged in response to glucocorticoids, indicating a primary effect of dexamethasone. Furthermore, cycloheximide by itself had no significant effect on ornithine decarboxylase mRNA levels. Inhibition of transcription with actinomycin D showed a half-life for ornithine decarboxylase mRNA of approximately 240 minutes. Ornithine decarboxylase mRNA stability was not affected by dexamethasone pretreatment for 12 hours. Therefore, these data suggest that dexamethasone regulates ODC gene expression via glucocorticoid receptor-mediated gene transcription. Furthermore, translational mechanisms seem to be involved in glucocorticoid-regulated ornithine decarboxylase induction.
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PMID:Glucocorticoids stimulate ornithine decarboxylase gene expression in pancreatic AR42J cells. 188 4

1. Glucocorticoid hormones affect several functions of the spinal cord, such as synaptic transmission, biogenic amine content, lipid metabolism, and the activity of some enzymes (ornithine decarboxylase, glycerolphosphate dehydrogenase), indicating that this tissue is a target of adrenal hormones. 2. Corticosterone, the main glucocorticoid of the rat, is detected at all regional levels of the spinal cord, and cold stress increases this steroid, predominantly in the cervical regions. 3. Intracellular glucocorticoid receptors have been found in the spinal cord, with higher concentrations in the cervical and lumbar enlargements. Prima facie, these receptors presented biochemical, stereospecifical, and physicochemical properties similar to those of receptors found in other regions of the nervous system. The prevalent form in the spinal cord is the type II receptor, although type I is also present in small amounts. 4. The type II glucocorticoid receptor of the spinal cord shows an affinity lower (Kd 3.5 nM) than that of the hippocampal type II site (Kd 0.7 nM) when incubated with [3H]dexamethasone. This condition may impair the nuclear translocation of the spinal cord receptor. 5. Another peculiar property of spinal cord type II site is a greater affinity for DNA-cellulose binding than the hippocampal receptor during heat-induced transformation. Also, the spinal cord receptor shows resistance to the action of RNAse A, an enzyme which increases DNA-cellulose binding of the hippocampal receptor, indicating that both receptors may be structurally different. 6. Therefore, it is possible that a different subclass of type II, or "classical glucocorticoid receptor," is present in the spinal cord. This possibility makes the cord a useful system for studying diversity of glucocorticoid receptors of the nervous system, especially the relationship between receptor structure and function.
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PMID:Adrenocorticoid action in the spinal cord: some unique molecular properties of glucocorticoid receptors. 266 68

The bovine adrenal medulla was investigated regarding the presence of glucocorticoid binding protein and the increases in ornithine decarboxylase (ODC) activity and epinephrine and norepinephrine by dexamethasone. Scatchard analysis of specific cytosol [3H] dexamethasone-binding study indicated a single class of high affinity (kd, 35 +/- 5 nM) and limited binding sites (150 +/- 26 fmoles/mg protein). Competition studies of various steroids indicated a high affinity for dexamethasone and hydrocortisone. Sedimentation in sucrose density gradients revealed a 7.3 S binding peak in the cytosol. Dexamethasone caused an increase in ornithine decarboxylase (ODC) activity within 1 to 2 hours after which the norepinephrine and epinephrine contents increased 16 hours after the peak of ODC activity in a dose dependent manner of dexamethasone in bovine adrenal medullary chromaffin cells in primary monolayer culture. These data suggest that the bovine adrenal medulla is a target organ of glucocorticoid hormone and that norepinephrine and epinephrine syntheses are regulated by a glucocorticoid receptor-mediated mechanism.
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PMID:Epinephrine and norepinephrine syntheses are regulated by a glucocorticoid receptor-mediated mechanism in the bovine adrenal medulla. 399 May 18

The effect of unilateral removal of the dorsal hippocampus and of glucocorticoid administration was measured on the activity of ornithine decarboxylase (ODC) in the remaining contralateral hippocampus lobe. Unilateral hippocampectomy (Hx) resulted in a rapid rise of ODC activity in the contralateral lobe. The effect on ODC was maximal at 6 h after surgery and lasted two days. In the absence of the adrenals the effect of Hx on the enzyme was more potent and more prolonged. Elevated ODC activity was still detectable at 5 days after surgery, but not at 10 days. Chronic replacement with dexamethasone (DEX) offered in drinking water decreased the Hx-induced ODC response of ADX rats at 3 days after surgery to the level of enzyme activity observed in the S-ADX Hx subject. The effect of the steroid seemed related to the extent of occupation of the pool of glucocorticoid receptor sites in cytosol of rat hippocampus. In contrast, a single injection of a high dose of DEX to Hx-ADX animals at 3 days after surgery increased ODC activity in addition to the lesion-induced ODC in the contralateral lobe. It is concluded that after unilateral removal of the dorsal hippocampus ODC is a biochemical marker for cellular responses taking place in the contralateral lobe. Glucocorticoids modulate the lesion-induced ODC response.
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PMID:Glucocorticoids modulate the response of ornithine decarboxylase to unilateral removal of the dorsal hippocampus. 662 81

Ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, was measured in the brain and the liver of adrenalectomized rats after an acute s.c. treatment with glucocorticoids. The effects of corticosterone and dexamethasone were compared in three brain areas, the cerebral cortex, hippocampus, and cerebellum. These structures have similar concentrations of cytosolic glucocorticoid receptor, as measured by an in vitro exchange assay using a specific glucocorticoid ligand, [3H]RU 26988, but contain different amounts of mineralocorticoid receptor. Corticosterone and dexamethasone increased ODC activity in the liver and brain areas in a dose-dependent manner, dexamethasone being more active than corticosterone in all tissues. Moreover, estradiol, progesterone, and testosterone were inactive. Aldosterone, at high doses, increased brain ODC activity. Glucocorticoids, selected for their weak binding, or lack of binding to the mineralocorticoid receptor, were tested and found to be highly active in inducing brain and liver ODC, thus showing that ODC induction by steroids is specific for glucocorticoids. These results are among the first to suggest biochemically a central action of glucocorticoids following an acute treatment and confirm that the brain is a glucocorticoid target organ.
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PMID:Ornithine decarboxylase induction by glucocorticoids in brain and liver of adrenalectomized rats. 706 53

The influence of sepsis on polyamine metabolism in the liver was studied in rats. Sepsis was induced by cecal ligation and puncture; control rats were sham-operated. Sepsis resulted in increased concentrations in liver tissue of putrescine and spermidine and stimulated activity of the enzymes ornithine decarboxylase (ODC) and s-adenosylmethionine decarboxylase. A similar metabolic response was seen following the subcutaneous injection of 1 mg/kg of endotoxin or following the e intraperitoneal injection of 100 micrograms/kg of human recombinant tumor necrosis factor (TNF)-alpha or interleukin-1 alpha (IL-1 alpha). ODC mRNA levels determined by Northern blots were increased in liver tissue of septic rats, suggesting that the increase in ODC activity may be regulated at the transcriptional level although increased stability of the messenger could give rise to similar results. Treatment of rats with either TNF antiserum, recombinant IL-1 receptor antagonist, or the glucocorticoid receptor antagonist RU 38486, did not prevent the sepsis-induced increase in hepatic ODC activity. The data suggest that sepsis stimulates the biosynthesis of polyamines in liver tissue and that this response to sepsis may not primarily be mediated by TNF, IL-1, or glucocorticoids. The biological role of increased liver polyamines during sepsis, in particular their relationship with the synthesis of acute phase proteins, remains to be determined.
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PMID:Sepsis stimulates polyamine biosynthesis in the liver and increases tissue levels of ornithine decarboxylase mRNA. 860 96

This study was conducted to determine a role for cortisol in regulating intestinal ornithine decarboxylase (ODC) activity and to identify the metabolic sources of ornithine for intestinal polyamine synthesis in suckling pigs. Thirty-two 21-day-old suckling pigs were randomly assigned to one of four groups with eight animals each and received daily intramuscular injections of vehicle solution (sesame oil; control), hydrocortisone 21-acetate (HYD; 25 mg/kg body wt), RU-486 (10 mg/kg body wt, a potent blocker of glucocorticoid receptors), or HYD plus RU-486 for two consecutive days. At 29 days of age, pigs were killed for preparation of jejunal enterocytes. The cytosolic fraction was prepared for determining ODC activity. For metabolic studies, enterocytes were incubated for 45 min at 37 degrees C in 2 ml of Krebs-bicarbonate buffer (pH 7.4) containing 1 mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U-(14)C]glutamine, or 1 mM [U-(14)C]proline plus 1 mM glutamine. Cortisol administration increased intestinal ODC activity by 230%, polyamine (putrescine, spermidine, and spermine) synthesis from ornithine and proline by 75-180%, and intracellular polyamine concentrations by 45-83%. Polyamine synthesis from arginine was not detected in enterocytes of control pigs but was induced in cells of cortisol-treated pigs. There was no detectable synthesis of polyamines from glutamine in enterocytes of all groups of pigs. The stimulating effects of cortisol on intestinal ODC activity and polyamine synthesis were abolished by coadministration of RU-486. Our data indicate that an increase in plasma cortisol concentrations stimulates intestinal polyamine synthesis via a glucocorticoid receptor-mediated mechanism and that proline (an abundant amino acid in milk) is a major source of ornithine for intestinal polyamine synthesis in suckling neonates.
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PMID:Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets. 1091 40

Several factors (including diets, changes in intestinal fluora, and hormones) regulate postnatal intestinal growth and development. Based on the early studies involving modification of the adrenal gland, pituitary gland or hypothalamus, exogenous glucocorticoids and glucocorticoid receptor antagonists are now used to study glucocorticoid-mediated metabolism of amino acids in the small intestine. Findings from these studies indicate that physiological levels of glucocorticoids stimulate the catabolism of glutamine and proline for the synthesis of citrulline and arginine in enterocytes during weaning. In addition, increases in circulating levels of glucocorticoids enhance expression of arginase, proline oxidase and ornithine decarboxylase, as well as polyamine synthesis from arginine and proline in enterocytes. These actions of the hormones promote intestinal maturation and may have therapeutic effects on intestinal disease (e.g., necrotizing enterocolitis). Molecular aspects, species-specific effects, and developmental responsiveness to glucocorticoids should be taken into consideration in designing both experimental and clinical studies.
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PMID:Glucocorticoid regulation of amino acid and polyamine metabolism in the small intestine. 1903 8


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