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Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity

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Abstract Aim:

To investigate the anti-implantation effect of droloxifene and study the possible relationship between the anti-estrogenic activity of droloxifene and its antiimplantation effect. Methods:

Pregnant rats were treated orally with droloxifene at 10:00 AM on d 2 at doses of 1.25–20 mg/kg to observe anti-implantation effects, and then doses of 14 mg/kg or 2.5 mg/kg were given at different time on d 2 to d 5 to determine the optimal administration time for anti-implantation effects. Pregnant rats were treated with a combination of droloxifene (2.5 mg/kg, ig) and E2 (0.5–8.0 g/kg, sc) on the optimal administration time to observe the antagonistic effect of external estrogen on the anti-implantation effect of droloxifene. Serum estrogen and progesterone levels were measured by carrying out radioimmunoassay on d 1 to d 6 in droloxifene-treated and control rats to determine the surge time for nidatory estrogen and the effect of droloxifene on ovary function. Results:

Droloxifene has anti-implantation effects in rats. The optimal oral administration time was at 22:00 PM on d 4, which was after the surge time for nidatory estrogen (on d 4 at 10:00 AM). This suggests that the anti-implantation effect of droloxifene is not attributable to antagonism of the surge in secretion of nidatory estrogen. External estrogen did not antagonize the anti-implantation effect of droloxifene. Droloxifene had no effect on the serum levels of estrogen and progesterone on d 5 or d 6 when administered on d 4 at 22:00 PM. Conclusion:

Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.
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Keywords: 3-hydroxytamoxifen; estrogen; implantation; progesterone; rats

Document Type: Research Article

Affiliations: Shanghai Institute of Materia Media, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 201203, China

Publication date: 2005-10-01

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