Changes in uterine ornithine decarboxylase activity and steroid receptor levels during decidualization in the rat induced by CDRI-85/287.

Abstract

CDRI-85/287 is an anti-estrogen and interferes with decidualization in the rat uterus. In this study, uterine estrogen receptor (ER) and progesterone receptor (PR) levels were determined during the inhibition of decidualization. The effect of 85/287 on uterine ornithine decarboxylate (ODC) activity (a marker enzyme for decidualization) was also studied, using immature ovariectomized rats divided into four different groups: control, 2.5mg/kg 85/287 only; 1 microg estradiol only; and 85/287 + estradiol. Pseudopregnant rats were administered 85/287 (2.5mg/kg p.o.) on day 3 post-coitum. Deciduoma was induced in one of the uterine horns on day 4 and animals were autopsied 18h post-traumatization. Both ERs and PRs showed an increase in traumatized horns compared with non-traumatized. In the 85/287-treated uterus, there was a reduction in cytosolic ERs in both traumatized horns. However, nuclear ER and PR levels increased in both horns under the influence of 85/287. Similarly, in a tamoxifen (0.03mg/kg)-treated group a decline was noticed in cytosolic ER with a mild increase in nuclear PR. Total ER content, expressed per 100 microg DNA, showed a decline in 85/287- or tamoxifen-treated rats. However, no significant alterations were observed in total PR levels in non-traumatized horns. In an immature rat model, 85/287 caused a significant (>50%) reduction in estradiol-induced ODC activity. These findings suggest that the decidualization inhibitory activity of 85/287 may be attributed to inhibition of certain timed biochemical events and genomic/non-genomic actions of estrogens in the rat uterus.