Polyamines in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney. Differential effect of alpha-difluoromethylornithine.
In the testosterone-induced hypertrophic and antifolate (N10-propargyl,5,6-dideazafolic acid, CB 3717)-induced hyperplastic mouse kidney models, a marked increase of two diamine levels--putrescine and cadaverine--occurred which paralleled induced ornithine decarboxylase (ODC) activity. Under these conditions the augmentation of spermidine levels was much smaller, while spermine levels were affected differentially--increased by testosterone and decreased by CB 3717; this resulted in an increase of spermidine/spermine ratio in hyperplastic, but not hypertrophic kidney. alpha-Difluoromethylornithine (DFMO) prevented testosterone- or CB 3717-induced increment of both diamine levels. Spermidine and spermine depletion in response to DFMO was significant in hyperplastic kidney only. DFMO also significantly affected the other biochemical markers of hyperplasia, namely lowered CB 3717-induced cell proliferation rate and increased S-adenosylmethionine decarboxylase (AdoMetDC) activity. In contrast, testosterone-induced hypertrophy was not influenced by DFMO, as judged by the lack of its effect on S-adenosylmethionine synthetase and cystathionine and synthase activity. These results indicate that the increase of putrescine levels does not mediate testosterone-induced renal hypertrophy and possibly also antifolate-induced hyperplasia. The involvement of spermidine in mediation of renal hyperplasia is highly possible, while that of spermine is excluded.
Manteuffel-Cymborowska
M
M
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Chmurzyńska
W
W
Grzelakowska-Sztabert
B
B
D000818:Animals; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives; D006965:Hyperplasia / Q000139:chemically induced; D006984:Hypertrophy / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D009929:Organ Size; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000032:analysis*; D011799:Quinazolines; D013739:Testosterone
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011799:Quinazolines; D013739:Testosterone; C031662:CB 3717; D005492:Folic Acid; D000518:Eflornithine