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

Abstract

1. 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. 2. In seminal vesicle, the inhibition of putrescine and spermidine accumulation, as well as ofornithine decarboxylase activity, was only minimal, and no stimulation of S-adenosylmethionine decarboxylase was observed. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.

Red blood cell polyamine levels and host toxicity during continuous alpha‐difluoromethylornithine infusion

“…There are several reports demonstrating the effect of DFMO on polyamine levels in tissues and cultured cell lines (Danzin et al, 1979;Kapyaho et al, 1984;Seppanen et al, 1981;Shirahata and Pegg, 1985). These studies have shown that DFMO produces a significant decrease in putrescine and spermidine levels and a slight increase or decrease in spermine levels.…”

Polyamines Increase in Human Peripheral Blood and Bone Marrow Mononuclear Cells following Administration of Methylglyoxal bis(guanylhydrazone)

“…This occurred even in patients in whom the DFMO was clearly acting effec tively as an ODC inhibitor, as evidenced by the decline achieved in the cellular po lyamine levels during the pretreatment period. Administration of MGBG to animals promotes large increases in the putrescine levels of rat intestinal mucosa [30], mouse brain [14], ventral prostate [18], spleens of LI210 leukemia-bearing mice [11], and transplantable prostate cancer [7], How ever, in contrast to the present findings in humans, all of the animal studies, except that done with ventral prostate, found that MGBG promoted a decrease or no change in tissue spermidine levels and little change in spermine levels. Administration of MGBG to animals promotes an in crease in tissue activities of both ODC [7,9,12,14,18,30] and AMeDC [9,15,18,27,30] providing a potential explanation for the increased cellular polyamines noted in the present study.…”