Modulation of rat uterine progesterone receptor levels and peroxidase activity by tamoxifen citrate, LY117018, and estradiol.

Abstract

The biochemical and morphological effects on the immature rat uterus of tamoxifen citrate (TAM) and LY117018 were compared with those of estradiol. A single dose of TAM (100 μg) increased uterine wet weight and peroxidase activity 12,24,36,48,60, and 72 h postinjection, while the uterine DNA content was increased after 36 h compared to controls at 72 h. A single sc dose of LY117018 (100 fig) also increased uterine wet weight and peroxidase activity, although to a lesser extent than TAM, 36–72 h postinjection. DNA content was increased to the same extent as that observed after TAM treatment. Coadministration of progesterone (1.0 mg) with 100 μg TAM or LY117018 completely blocked the antiestrogen-induced increase in uterine peroxidase activity and elongation of the luminal epithelium observed at 36 h, while the increase in uterine wet weight was only partially blocked. Cytosol progesterone receptor (PR) levels were increased significantly at 36 h by estradiol (10 μg) or TAM (100 μg), but no increase was obs...