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

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.

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

Biochemical Journal ◽

10.1042/bj1920059 ◽

1980 ◽

Vol 192 (1) ◽

pp. 59-63 ◽

Cited By ~ 17

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.

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Regulation of l-ornithine decarboxylase and S-adenosyl-l-methionine decarboxylase in rat ventral prostate and seminal vesicle

Biochemical Journal ◽

10.1042/bj1680379 ◽

1977 ◽

Vol 168 (3) ◽

pp. 379-385 ◽

Cited By ~ 26

Author(s):

Kirsti Piik ◽

Pirkko Rajamäki ◽

Sujit K. Guha ◽

Juhani Jänne

Keyword(s):

Enzyme Activity ◽

Seminal Vesicle ◽

Ornithine Decarboxylase ◽

Prostate Gland ◽

Ventral Prostate ◽

Rat Tissues ◽

Decarboxylase Activity ◽

Testosterone Treatment ◽

Ornithine Decarboxylase Activity ◽

Stimulation Of

1. The activities of l-ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50) were dramatically enhanced in both the ventral prostate and the seminal vesicle of castrated rats in response to androgenic stimulation. The time course of the stimulation of ornithine decarboxylase together with the quantitatively different response of adenosylmethionine decarboxylase to testosterone treatment in the prostate gland and seminal vesicle indicated that the enhancement in polyamine synthesis in the ventral prostate may reflect both cellular proliferation and the restoration of the secretory functions of the organ. In the seminal vesicle, however, the stimulation of the polyamine-biosynthetic pathway more closely resembled the pattern found in other rat tissues, such as regenerating liver, undergoing compensatory growth. 2. Ornithine decarboxylase activity in the ventral prostate and especially in the seminal vesicle of sexually mature rat was diminished in vivo by various short-chain diamines such as 1,2-diaminoethane, 1,3-diaminopropane and putrescine (1,4-diaminobutane). These diamines had no direct effect on the enzyme activity in vitro. 3. In contrast with the marginal decrease in ornithine decarboxylase activity produced by diaminoethane in the ventral prostate of non-castrated animals, repeated injections of the latter amine completely prevented the intense stimulation of the enzyme activity in the ventral prostate and seminal vesicle of castrated rats at 24h after the commencement of testosterone treatment. 4. The decrease in ornithine decarboxylase activity observed after injections of diamines (putrescine) in the ventral prostate was apparently associated with a similar decrease in the amount of immunoreactive protein as revealed by immunotitration of the enzyme with antiserum to rat ornithine decarboxylase.

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

Biochemical Journal ◽

10.1042/bj1660081 ◽

1977 ◽

Vol 166 (1) ◽

pp. 81-88 ◽

Cited By ~ 19

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

Biochemical Journal ◽

10.1042/bj1960733 ◽

1981 ◽

Vol 196 (3) ◽

pp. 733-738 ◽

Cited By ~ 14

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).

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