Open AccessAnti‐implantation effect of droloxifene in rats and its relationship with anti‐estrogenic activity 1
Author(s) -
HUANG Yong,
SHEN Yu,
FENG Ying,
CAO Lin,
LENG Ying
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00191.x
Subject(s) - estrogen , endocrinology , chemistry , medicine , oral administration , ovary , biology
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 μg/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.