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, 2.5 mg/kg 85/287 only; 1 mg estradiol only; and 85/287 þ estradiol. Pseudopregnant rats were administered 85/287 (2.5 mg/kg p.o.) on day 3 post-coitum. Deciduoma was induced in one of the uterine horns on day 4 and animals were autopsied 18 h 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 (0.03 mg/kg)-treated group a decline was noticed in cytosolic ER with a mild increase in nuclear PR. Total ER content, expressed per 100 mg DNA, showed a decline in 85/287-or tamoxifentreated 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.

Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran, a potent antiestrogenic agent in rats

“…Although these agents (tamoxifen and ormeloxifene) have low binding affinity for ER (2%-5%), their biologically active metabolites possess considerably high affinity for ER (comparable to E 2 ) (35,19). In view of the efficacy of K-1 as an antiestrogen specifically at the receptor level, it is important to emphasize its antifertility potential as compounds belonging to benzopyrans earlier have shown promise as antideciduogenic agents in rodent and primate species (36,37). However, the biological profile of its metabolites needs further investigation.…”

Prolactin signaling through the short isoform of the mouse prolactin receptor regulates DNA binding of specific transcription factors, often with opposite effects in different reproductive issues

“…ODC activity is associated with the rate of growth [ 59 ]. Since tissue growth is an essential step in the process of decidualization, ODC is considered as marker enzyme for decidualization [ 60 ]. PRL is known to stimulate ODC expression as well as enzyme activity [ 23 ].…”

Exploring polyamines: Functions in embryo/fetal development

“…At the sites of implantation, ODC1 expression gene is overactivated in mouse uterus after induction of estrogen ( Zhao et al., 2008 ). In addition, induction of estrogen antagonists decrease the ODC1 gene expression in mouse and rat uterus respectively ( Zhao et al., 2008 , Dwivedi et al., 1999 ). However, this effect has not been observed in rodents due to the ODC1 activity which is considerably exceeding in humans endometrium under the follicular phase rather than luteal phase ( Holinka and Gurpide, 1985 ).…”