Ornithine Decarboxylase Activity In Rat Liver Research Articles

Blockade of α-and β-adrenergic receptors can prevent stimulation of liver ornithine decarboxylase activity by glucocorticoid or laparatomy

Rat liver ornithine decarboxylase induction by dexamethasone or laparatomy, which is dramatically impaired by catecholamine depletion, is not affected by α-and β-adrenergic blockers administered simultaneously 1 h prior to steroid injection or operation. However, if blockade is maintained for 24 h, an effect comparable to that of catecholamine depletion is obtained. Reciprocally, the response of the decarboxylase to catecholamines is severely compromised in adrenalectomized rats. Under the same conditions, induction of tyrosine aminotransferase by dexamethasone is not significantly affected by catecholamine availability, which altogether demonstrates that rat liver ornithine decarboxylase activity is specifically governed by the interaction between glucocorticoids and catecholamines.

Cell-free synthesis of ornithine decarboxylase. Changes in mRNA activity in the liver of thioacetamide-treated rats.

Ornithine decarboxylase (ODC)mRNA associated with free polysomes of rat liver was translated in a reticulocyte lysate cell-free system. Newly synthesized ODC protein was identified by specific immunoprecipitation, molecular size as determined by polyacrylamide gel electrophoresis with sodium dodecyl sulfate, and competition by excess unlabeled ODC in the immunoprecipitation. A single injection of thioacetamide was found to cause several fold increases in both immunotitratable ODC protein and polysomal ODC-mRNA activity, while it provoked a much larger increase in ODC activity in rat liver. The results indicate that the induction of hepatic ODC activity by thioacetamide treatment is due not only to an increase in the activity of polysomal ODC-mRNA but also to a translational and/or posttranslational control.

Effect of chloroform on hepatic and renal DNA synthesis and ornithine decarboxylase activity in mice and rats

Chloroform administered intraperitoneally (i.p.) to male mice and rats resulted in a dose-dependent increase in hepatic ornithine decarboxylase (ODC) activity. Maximal induction of the enzyme in mice was 10-fold and occurred at 375 mg/kg chloroform; in rats it was 52-fold and occurred at 750 mg/kg chloroform. Chloroform increased in mice and decreased in rats the rate of hepatic and renal DNA synthesis. Therefore, the induction of ODC activity in rat liver was not followed with an increase in DNA synthesis. The implications of these results to the proposed nongenetic mechanism of chloroform induction of hepatocellular carcinoma in mice and renal tumors in rats are discussed.

Induction of Ornithine Decarboxylase and Augmentation of Tyrosinc Aminotransferase Activity by N-Hydroxy-2-acetylaminofluorene and 2-Acctylaminofluorene in Rat Liver. Influence of Sex, Retinylacetate, Indomethacin, and Pentachlorophenol

IP injection in rats of 2-acetylaminofluorene (AAF) or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) resulted in a transient increase of hepatic ornithine decarboxylase (ODC) and tyrosine aminotransferase (TAT) activity. Maximal activity of ODC was observed 4 hr and of TAT 3 hr after administration of either AAF or N-OH-AAF. A lag-time of 2 hr preceded the increase of ODC and TAT activity. N-OH-AAF dependent ODC induction displayed an almost linear dose-response in the dose range up to 94.1 mumol/kg bw (body weight) when the ODC activity was measured at its maximum 4 hr after administration. Elevation of the dose N-OH-AAF to 126 mol/kg bw resulted in a lower ODC induction. Administration of doses AAF to 31.4 mumol did not change ODC activity. At doses up to 126 mumol/kg bw ODC induction increased linear. TAT induction increased linear in the dose range 15.7-94.1 mumol N-OH-AAF and 31.4-94.1 mumol AAF/kg. Lowering the dose of AAF did not result in a lower ODC or TAT activity. Judged by the effects of actinomycin D or cycloheximide administered 1 hr prior to AAF or N-OH-AAF, the in vivo induction of rat liver ODC activity by AAF and N-OH-AAF appeared to be under transcriptional control, whereas augmentation of TAT activity under influence of AAF or N-OH-AAF appeared the result of (post) translational events. Induction of ODC by AAF or N-OH-AAF was not significantly changed by indomethacin, was slightly increased by pentachlorophenol (PCP) and was synergistically enhanced by retinylacetate (RA). The increase of TAT activity was stimulated by PCP and RA. The effect of PCP indicates that N-sulfonoxy-2-acetylaminofluorene is most probably not involved in the induction of ODC. AAF appeared more effective hepatic ODC inducer in females than males and moreover more effective than N-OH-AAF in females. N-OH-AAF had stronger ODC inducing capacity in males than females. Similar observations were made with respect to TAT activity. When induction of ODC is indicative for a tumor promoting property then the data presented here suggest that tumor promotion of the complete carcinogens AAF and N-OH-AAF is not mediated by N-O-sulfation; this might be due to other metabolic conversions.

Comparison of enhancement of GGTase-positive foci and induction of ornithine decarboxylase in rat liver by barbiturates.

The indication of ornithine decarboxylase (ODC) by barbiturates and the ability of barbiturates to enhance neoplastic progression of chemically initiated cancer was examined in rat liver. All seven barbiturates induced ODC with barbital (7.7 fold increase) and phenobarbital (5.7 fold increase) demonstrating the most potent activity. Maximum induction of ODC by phenobarbital was obtained in 18 h. Barbital (500-5000 p.p.m.) and phenobarbital (500 p.p.m.) administered in the drinking water enhanced the appearance of diethylnitrosamine (DENA)-initiated gamma- glutamyltranspeptidase (GGTase)-positive foci. Amobarbital, hexabarbital and pentabarbital did not enhance the appearance of GGTase-positive foci. In the absence of previous initiation by DENA, the enhancing regimen of the barbiturates did not cause the appearance of GGTase-positive foci. Barbiturates induced ODC activity in rat liver and enhanced the incidence of DENA initiated GGTase-positive foci.

Differential effects of placental lactogen, growth hormone and prolactin on rat liver ornithine decarboxylase activity in the perinatal period

Ovine placental lactogen, (oPL), ovine growth hormone, (oGH), and ovine prolactin, (oPRL) are present in high concentrations in the fetal circulation late in gestation. To determine if these hormones stimulate the activity of ornithine decarboxylase (ODC), an enzyme widely implicated in the control of cellular growth, rat fetuses were injected in utero with 100 μg of oPL, oGH, oPRL, rat growth hormone (rGH) or rat prolactin (rPRL) and ODC activity in the livers, hearts, and brains of the fetuses was measured 2, 4, and 6 hours after injection. OPL stimulated fetal liver ODC activity by 282 ± 45% (mean ± SEM) as compared to litter mates injected with buffer alone but oGH, oPRL, rGH and rPRL had no effect on fetal liver ODC activity. However, in neonatal rats 24–48 hours old all five hormones significantly increased liver ODC activity. ODC activities in the hearts and brains of the fetuses and neonates were unaffected by any of the five hormones. In other experiments 50 μg of oPL significantly stimulated fetal liver ODC activity while 250 μg of oGH were without effect. However 25 μg of oGH significantly stimulated liver ODC activity in rat pups 1–2 days after birth. These results suggest that oPL, by its stimulation of ODC activity, has somatotropic effects in the fetus and that rat liver ODC activity becomes responsive to growth hormone and prolactin in the perinatal period.

Effects of aliphatic diamines on rat liver ornithine decarboxylase activity.

Rat liver ornithine decarboxylase activity was decreased by administration of putrescine (1,4-diaminobutane) or other diamines, including 1,3-diaminopropane, 1,5-diaminopentane and 1,6-diaminohexane. This effect was seen in control rats and in rats in which hepatic ornithine decarboxylase activity had been increased by administration of growth hormone (somatotropin) or thioacetamide. Loss of activity was not dependent on the conversion of putrescine into polyamines and was short-lived. Within 6h after intraperitoneal administration of 0.8 mmol/kg body wt., ornithine decarboxylase activity had returned to normal values. This return correlated with the rapid loss of the diamines from the liver, and the decrease in activity could be slightly prolonged by treatment with aminoguanidine, a diamine oxidase inhibitor. A decrease in ornithine decarboxylase activity by these diamines was accompanied by the accumulation in the liver of a nondiffusible inhibitor that decreased the activity of a purified ornithine decarboxylase preparation. The possibility that administration of non-physiological diamines that are not converted into polyamines might be useful for the inhibition of polyamine synthesis is discussed.

Changes in rat liver ornithine decarboxylase activity during ageing and effect of stimulation by dexamethasone

We have studied the ornithine decarboxylase activity in the liver of 1, 3 and 24 months old rats: such activity has a dramatic diminuation in the age range from 1 to 3 months, but the activity at 24 months is significantly higher than that at 3 months. The treatment with Dexamethasone causes a very remarkable elevation in the activity of ornithine decarboxylase, up to rates that are not significantly different for the three ages.

The [formula omitted] stimulation of rat liver ornithine decarboxylase activity by dibutyryl cyclic adenosine 3′,5′-monophosphate, theophylline and dexamethasone

The hepatic ornithine decarboxylase (ODC) activity of normal rats was stimulated more than 7-fold 3 hours after a single intraperitoneal injection of dibutyryl cyclic adenosine 3′,5′-monophosphate (dibu-cAMP). The 3-hour ODC activity was also stimulated by single injections of either theophylline or dexamethasone (10- and 21-fold, respectively). The simultaneous administration of actinomycin D with either dibu-cAMP, theophylline or dexamethasone reduced the 3-hour ODC activity by 91, 62 and 58 percent, respectively. When actinomycin D was given one hour after dibu-cAMP, no inhibition of ODC activity was observed.

The control of ornithine decarboxylase activity during liver regeneration

The effect of amino acids and growth hormone on rat liver ornithine decarboxylase activity was investigated in an attempt to elucidate the mechanisms that control the activity of this enzyme during the early stages of liver regeneration. A single administration of casein hydrolyzate to intact rats produces a marked increase in liver ornithine decarboxylase activity. The casein effect is abolished by puromycin or actinomycin, is not modified by adrenalectomy and is slowed down by hypophysectomy. Histidine also causes a rapid increase in the activity of the enzyme but the amino acid effect is blocked by puromycin, is not inhibited by actinomycin, and is entirely absent in hypophysectomized rats. Growth hormone injections increase ornithine decarboxylase activity in normal or regenerating liver. The action of the hormone is only slightly inhibited by doses of actinomycin that prevent any increase in the specific activity of nuclear or cytoplasmic rapidly labeled RNA. 8-Azaguanine injection or small doses of actinomycin do not block the initial increase in ornithine decarboxylase activity occurring shortly after partial hepatectomy. The possibility that a post-transcriptional mechanism is involved in the control of ornithine decarboxylase activity during liver regeneration is discussed in detail.