Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity.
OBJECTIVE
To investigate the anti-implantation effect of droloxifene and study the possible relationship between the anti-estrogenic activity of droloxifene and its anti-implantation 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 microg/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 radioimmunoassays 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.


CONCLUSIONS
Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.
Huang
Yong
Y
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.
Shen
Yu
Y
Feng
Ying
Y
Cao
Lin
L
Leng
Ying
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood*; D005260:Female; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013995:Time
D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; C038345:droloxifene; D011374:Progesterone; D004958:Estradiol