Relationships among uterine growth, ornithine decarboxylase activity and polyamine levels: studies with estradiol and antiestrogens.
We have examined the effects of estradiol (E2) and antiestrogen (AE) on ornithine decarboxylase (ODC) activity and uterine polyamine concentrations as an aid to understanding the dissimilar effects of E2 and AE on uterine growth. ODC activity rises rapidly from very low levels in immature (day 20-23) rat uteri, showing two markedly (approximately 500-fold) increased peaks of activity at 5 h and 16 h after E2 (2 micrograms) injection. After AE (50 micrograms CI628 or U23469) treatment, the temporal increase in ODC activity is slow and only one major peak is found at 24 h. Daily injections of E2 over a 3-day period evoke continued stimulation of uterine ODC activity; however, the same daily treatment regimen with AE results in stimulation of ODC activity only during the first day. After pretreatment with AE, E2 can still elicit the early (5 h) peak of ODC activity, but the later (16 h) peak of ODC activity is blocked. Quantitation of uterine polyamines by high performance liquid chromatography reveals a 1.5-2-fold increase in the concentration of spermidine after 1 day of E2 or AE exposure, with little change in putrescine or spermine levels. After 3 days of E2, AE, or E2 plus AE treatment, spermidine concentrations are elevated 2-2.5-fold and spermine concentrations are elevated 1.5-fold. Putrescine concentrations are unchanged. Hence, regardless of the different degree to which the uterus is stimulated to grow in response to E2 and/or AE, there are corresponding changes in uterine ODC activity, such that polyamine concentrations are elevated to a similar extent in the E2- or AE-treated uterus.
D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D009594:Nitromifene / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D004965:Estrogen Antagonists; D011073:Polyamines; D013764:Tetrahydronaphthalenes; C014291:U 23469; D004958:Estradiol; D009594:Nitromifene; D009955:Ornithine Decarboxylase