scholarly journals Effect on prostatic growth of 2-difluoromethylornithine, an effective inhibitor of ornithine decarboxylase

1982 ◽  
Vol 202 (1) ◽  
pp. 175-181 ◽  
Author(s):  
C Danzin ◽  
N Claverie ◽  
J Wagner ◽  
J Grove ◽  
J Koch-Weser
Keyword(s):  
Ornithine Decarboxylase ◽  
Ventral Prostate ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Adenosylmethionine Decarboxylase ◽  
Dna Contents ◽  
Wet Weight ◽  
Rna And Dna

2-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, causes marked changes in the polyamine metabolism of ventral prostate when given to adult rats in drinking water (20 g/l) for 3 consecutive days. A 90% inhibition of ornithine decarboxylase activity is accompanied by approx. 80% decreases of the concentrations of putrescine and spermidine and by a 36% decrease in spermine. Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold. When DFMO is given to immature rats for 12 consecutive days the above described changes are accompanied by a marked reduction in the age-dependent increases of the wet weight and RNA and DNA contents of the ventral prostate. In adult rats DFMO decreases the weight and RNA content of the ventral prostate within 4 days by 32% and 24% respectively and maintains them constant for the next 19 days. After 23 days of treatment, the prostatic weight is 46% of that of control animals of the same age, whereas the weights of other organs are only slightly decreased. Cytological studies carried out at this time show that DFMO reduces the size of both prostatic acini and the epithelial cells lining the acini.

scholarly journals Response of enzymes involved in the metabolism of polyamines to phytohaemagglutinin-induced activation of human lymphocytes

1981 ◽  
Vol 196 (3) ◽  
pp. 733-738 ◽  
Author(s):  
H Korpela ◽  
E Hölttä ◽  
T Hovi ◽  
J Jänne
Keyword(s):  
Ornithine Decarboxylase ◽  
Human Lymphocytes ◽  
Lymphocyte Activation ◽  
Decarboxylase Activity ◽  
Spermidine Synthase ◽  
Irreversible Inhibitor ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Diamine Oxidase Activity ◽  
Stimulation Of

The stimulation of lymphocyte ornithine decarboxylase and adenosylmethionine decarboxylase produced by phytohaemagglutinin was accompanied by an equally marked, but delayed, stimulation of spermidine synthase, which is not commonly considered as an inducible enzyme. In contrast with the marked stimulation of these biosynthetic enzymes, less marked changes were observed in the biodegradative enzymes of polyamines in response to phytohaemagglutinin. Diamine oxidase activity was undetectable during all stages of the transformation. The activity of polyamine oxidase remained either constant or was slightly decreased several days after addition of the mitogen. The activity of polyamine acetylase (employing all the natural polyamines as substrates) distinctly increased both in the cytosolic and crude nuclear preparations of the cells during later stages of mitogen activation. Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, although powerfully inhibiting ornithine decarboxylase, produced a gradual enhancement of adenosylmethionine decarboxylase activity during lymphocyte activation, without influencing the activities of the two propylamine transferases (spermidine synthase and spermine synthase).

scholarly journals The influence of nerve section on the metabolism of polyamines in rat diaphragm muscle

1981 ◽  
Vol 196 (2) ◽  
pp. 603-610 ◽  
Author(s):  
D Hopkins ◽  
K L Manchester
Keyword(s):  
Ornithine Decarboxylase ◽  
Normal Values ◽  
Methionine Adenosyltransferase ◽  
Diaphragm Muscle ◽  
Regulatory Mechanisms ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Rat Diaphragm ◽  
Nerve Section ◽  
Adenosylmethionine Decarboxylase

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed.

scholarly journals Differential effects of 2-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the testosterone-induced growth of ventral prostate and seminal vesicles of castrated rats

1984 ◽  
Vol 219 (3) ◽  
pp. 811-817 ◽  
Author(s):  
K Käpyaho ◽  
A Kallio ◽  
J Jänne
Keyword(s):  
Seminal Vesicle ◽  
Ornithine Decarboxylase ◽  
Seminal Vesicles ◽  
Ventral Prostate ◽  
Decarboxylase Activity ◽  
Adenosylmethionine Decarboxylase ◽  
Ornithine Decarboxylase Activity ◽  
Combined Use ◽  
Sexual Glands ◽  
Stimulation Of

2-Difluoromethylornithine totally prevented any increases in putrescine and spermidine concentrations in the ventral prostate of castrated rats during a 6-day testosterone treatment. Prostatic ornithine decarboxylase activity was inhibited by 80%, whereas S-adenosylmethionine decarboxylase was stimulated by more than 9-fold. In seminal vesicle, the inhibition of putrescine and spermidine accumulation, as well as of ornithine decarboxylase activity, was only minimal, and no stimulation of S-adenosylmethionine decarboxylase was observed. Administration of methylglyoxal bis(guanylhydrazone) to castrated androgen-treated rats resulted in a marked increase in concentrations of all prostatic polyamines. Prostatic ornithine decarboxylase activity was nearly 2 times and adenosylmethionine decarboxylase activity 9 times higher than that of the testosterone-treated animals. In contrast with ventral prostate, methylglyoxal bis(guanylhydrazone) treatment inhibited moderately the accumulation of spermidine and spermine in seminal vesicle, although both ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were stimulated. Difluoromethylornithine inhibited significantly the weight gain of ventral prostate, but methylglyoxal bis(guanylhydrazone) produced a substantial increase in prostatic weight. These changes were largely due to the fact that the volume of prostatic secretion was greatly decreased by difluoromethylornithine, whereas methylglyoxal bis(guanylhydrazone) increased the amount of secretion. Treatment with difluoromethylornithine strikingly increased the methylglyoxal bis(guanylhydrazone) content of both ventral prostate and seminal vesicle, but even under these conditions the drug concentration remained low in comparison with other tissues. The results indicate that a combined use of these two polyamine anti-metabolites does not necessarily result in a synergistic growth inhibition of the androgen-induced growth of male accessory sexual glands.

scholarly journals Role of propylamine transferases in hormone-induced stimulation of polyamine biosynthesis

1980 ◽  
Vol 192 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Kirsti Käpyaho ◽  
Hannu Pösö ◽  
Juhani Jänne
Keyword(s):  
Seminal Vesicle ◽  
Ornithine Decarboxylase ◽  
Ovarian Tissue ◽  
Ventral Prostate ◽  
Decarboxylase Activity ◽  
Spermidine Synthase ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Stimulation Of

The effect of various hormones on the activities of the four enzymes engaged with the biosynthesis of the polyamines has been investigated in the rat. Human choriogonadotropin induced a dramatic, yet transient, stimulation of l-ornithine decarboxylase (EC 4.1.1.17) activity in rat ovary, with no or only marginal changes in the activities of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (aminopropyltransferase; EC 2.5.1.16) or spermine synthase. A single injection of oestradiol into immature rats maximally induced uterine ornithine decarboxylase at 4h after the injection. This early stimulation of ornithine decarboxylase activity was accompanied by a distinct enhancement of adenosylmethionine decarboxylase activity and a decrease in the activities of spermidine synthase and spermine synthase. In the seminal vesicle of castrated rats, testosterone treatment elicited a striking and persistent stimulation of ornithine decarboxylase and adenosylmethionine decarboxylase activities. The activity of spermidine synthase likewise rapidly increased between the first and the second day after the commencement of the hormone treatment, whereas the activity of spermine synthase remained virtually unchanged during the whole period of observation. Testosterone-induced changes in polyamine formation in the ventral prostate were comparable with those found in the seminal vesicle, with the possible exception of a more pronounced stimulation of spermidine synthase activity. It thus appears that an enhancement in one or both of the propylamine transferase (aminopropyltransferase) activities in response to hormone administration is an indicator of hormone-dependent growth (uterus and the male accessory sexual glands), and is not necessarily associated with non-proliferative hormonal responses, such as gonadotropin-induced luteinization of the ovarian tissue.

scholarly journals Polyamine metabolism in liver of young rats

1978 ◽  
Vol 174 (3) ◽  
pp. 727-732 ◽  
Author(s):  
M E Brosnan ◽  
G W Symonds ◽  
D E Hall ◽  
D L Symonds
Keyword(s):  
Fold Increase ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Adult Rats ◽  
Adenosylmethionine Decarboxylase ◽  
Dna And Rna ◽  
Rat Pups ◽  
Old Rats ◽  
Rna Accumulation ◽  
Number Of Cells

Rat liver undergoes a phase of rapid growth during weaning. We followed the changes in polyamine metabolism occurring during this period of natural growth, and compared them with changes in DNA and RNA accumulation. There was a 2.5-fold increase in the number of cells per liver between suckling (18–19 days old) and weaning (30–32 days old) rats. Ornithine decarboxylase activity increased from the low value in 18-day-old rat pups and remained significantly higher (approx. 5–10-fold) than that in adult rats from day 21 to day 34. Putrescine-dependent S-adenosylmethionine decarboxylase activity was slightly but significantly increased during most of this period. Spermidine and RNA concentrations fluctuated in concert, whereas spermine content per cell doubled during the period from day 23 to day 30.

Inhibition of ornithine decarboxylase does not prevent intestinal smooth muscle hyperplasia in the rat

1994 ◽  
Vol 267 (6) ◽  
pp. G1021-G1027
Author(s):  
M. S. Luck ◽  
P. Bass
Keyword(s):  
Smooth Muscle ◽  
Dna Synthesis ◽  
Ornithine Decarboxylase ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Polyamine Metabolism ◽  
Intestinal Smooth Muscle ◽  
Irreversible Inhibitor ◽  
Maximal Peak ◽  
Wet Weight

The objective of this research is to examine the relationship between intestinal smooth muscle cell proliferation and polyamine metabolism. Proliferation of muscle is induced by serosal application of benzyldimethyltetradecylammonium chloride (BAC) to a segment of rat jejunum. This treatment destroys all of the longitudinal muscle, one-half of the circular muscle, and the myenteric and extrinsic nerves. The remaining muscle cells undergo mitosis and, by 15 days, the number of muscle cells is increased in both the longitudinal and circular muscle layers. Within 12 h after BAC treatment, there is an increase in the activity of ornithine decarboxylase (ODC) that returns to preinjury levels by 4 days. The smooth muscle content of the three polyamines putrescine, spermidine, and spermine is increased 6 h after injury, returning to preinjury levels within 1 day. DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, prevents the transient increases in both ODC activity and the three polyamines in the smooth muscle. In addition to preventing the transient increases in the three polyamines, DMFO has different effects on smooth muscle content of putrescine, spermidine, and spermine. Putrescine content is permanently depleted by DFMO. Spermidine and spermine content is initially decreased within 24 h by DFMO administration. In contrast to the persistent depletion of putrescine by DFMO, spermidine and spermine return to preinjury levels by 2 days. The maximal peak in DNA synthesis occurs 2 days after injury. In DFMO-administered animals, the maximal DNA synthesis occurs 5 days after injury. The increases in smooth muscle wet weight and DNA content 15 days after injury are not affected by DFMO.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on testosterone-induced regeneration of prostate and seminal vesicle in castrated rats

1979 ◽  
Vol 180 (3) ◽  
pp. 507-513 ◽  
Author(s):  
Charles Danzin ◽  
Michel J. Jung ◽  
Nicole Claverie ◽  
Jeffrey Grove ◽  
Albert Sjoerdsma ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Seminal Vesicle ◽  
Ornithine Decarboxylase ◽  
Normal Values ◽  
Ventral Prostate ◽  
Clear Correlation ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Androgen Treatment ◽  
Repeated Doses

1. Castration of adult rats markedly decreases the amounts of polyamines (putrescine, spermidine and spermine) and of RNA and DNA in the ventral prostate and the seminal vesicle. 2. Daily injections of testosterone propionate to rats castrated 7 days previously increase polyamine and nucleic acid contents more rapidly in the seminal vesicle than in the ventral prostate. 3. After 7 days of androgen treatment, polyamine and nucleic acid contents of the seminal vesicle are significantly higher than those of intact animals. Nucleic acid, but not polyamine, contents return to normal values during the next 4 days of continued treatment. In the prostate, androgen treatment increases polyamine and nucleic acid contents to, but not above, normal values. 4. Repeated doses of α-difluoromethylornithine, a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, totally blocked the testosterone-induced increase of putrescine and spermidine in the ventral prostate and of putrescine in the seminal vesicle. They slowed significantly the accumulation of spermine in the ventral prostate and of spermidine in the seminal vesicle. α-Difluoromethylornithine also retarded the testosterone-induced accumulation of RNA in the ventral prostate. However, no clear correlation was apparent between accumulation of polyamines and of nucleic acids in the two organs. 5. α-Difluoromethylornithine markedly slows the testosterone-induced weight gain of the prostate, but not of the seminal vesicle. Cytological studies suggest that this effect on the prostate is due to inhibition of the androgen-induced restoration of the secretion content of prostatic acini.

Hormonal regulation of postprandial induction of gastrointestinal ornithine decarboxylase activity

1986 ◽  
Vol 251 (4) ◽  
pp. G460-G466
Author(s):  
E. R. Seidel
Keyword(s):  
Ornithine Decarboxylase ◽  
Hormonal Regulation ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Growth Activity ◽  
Epidermal Growth ◽  
Elemental Diets ◽  
Mucosal Growth ◽  
Glyceryl Trioleate ◽  
Fasted Rats

The growth of gastrointestinal mucosa can be related to ingestion and digestion of diet, with fasting producing mucosal hypoplasia and hyperphagia producing mucosal hyperplasia. Experiments were designed to determine whether induction of polyamine metabolism following ingestion of a meal was related to mucosal growth. Activity of the enzyme ornithine decarboxylase (ODC) in both jejunum and ileum but not in duodenum was dependent on the presence of food in the gut; ODC activity was more than 200-fold greater in mucosa of fed rats than in fasted rats. Inhibition of ODC with difluoromethylornithine lead to mucosal atrophy in ileum but not in duodenum. Refeeding of fasted rats resulted in significant induction of ODC in duodenal, ileal, and colonic, but not fundic, mucosa. In addition, two hormones, epidermal growth factor and glucagon, were effective inducers of ileal ODC activity. Direct evidence for hormonal involvement in the postprandial rise in mucosal ODC activity was provided by experiments in rats that had undergone ileal bypass surgery. After refeeding of fasted rats mucosal ODC activity was induced in both ileum left in continuity and in the bypassed segment. Refeeding of elemental diets demonstrated that ingestion of carbohydrate alone was sufficient for maximal enzyme induction. Mixed amino acids or glyceryl trioleate were no more effective inducers than nonnutritive solutions of cellulose or saccharin. These data demonstrate that hormones which are released during ingestion and digestion of a meal are the stimuli for induction of mucosal polyamine metabolism, suggesting that food-induced mucosal growth is hormonally mediated.

scholarly journals Role of pyridoxal phosphate in mammalian polyamine biosynthesis. Lack of requirement for mammalian S-adenosylmethionine decarboxylase activity

1977 ◽  
Vol 166 (1) ◽  
pp. 81-88 ◽  
Author(s):  
A E Pegg
Keyword(s):  
Ornithine Decarboxylase ◽  
Pyridoxal Phosphate ◽  
Vitamin B ◽  
Decarboxylase Activity ◽  
Deficient Diet ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Ornithine Decarboxylase Activity

1. Polyamine concentrations were decreased in rats fed on a diet deficient in vitamin B-6. 2. Ornithine decarboxylase activity was decreased by vitamin B-6 deficiency when assayed in tissue extracts without addition of pyridoxal phosphate, but was greater than in control extracts when pyridoxal phosphate was present in saturating amounts. 3. In contrast, the activity of S-adenosylmethionine decarboxylase was not enhanced by pyridoxal phosphate addition even when dialysed extracts were prepared from tissues of young rats suckled by mothers fed on the vitamin B-6-deficient diet. 4. S-Adenosylmethionine decarboxylase activities were increased by administration of methylglyoxal bis(guanylhydrazone) (1,1′-[(methylethanediylidine)dinitrilo]diguanidine) to similar extents in both control and vitamin B-6-deficient animals. 5. The spectrum of highly purified liver S-adenosylmethionine decarboxylase did not indicate the presence of pyridoxal phosphate. After inactivation of the enzyme by reaction with NaB3H4, radioactivity was incorporated into the enzyme, but was not present as a reduced derivative of pyridoxal phosphate. 6. It is concluded that the decreased concentrations of polyamines in rats fed on a diet containing vitamin B-6 may be due to decreased activity or ornithine decarboxylase or may be caused by an unknown mechanism responding to growth retardation produced by the vitamin deficiency. In either case, measurements of S-adenosylmethionine decarboxylase and ornithine decarboxylase activity under optimum conditions in vitro do not correlate with the polyamine concentrations in vivo.

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