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 (~ 500-fold) increased peaks of activity at 5 h and 16 h after E₂ (2 μg) injection. After AE (50 μg 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.