No abstract

It is likely that mifepristone or levonorgestrel in the future will find extended use for contraceptive purposes. It is therefore essential to characterize the modes of action of these compounds. To assess the effect on the human Fallopian tube, 24 women with regular menstrual cycles and proven fertility, admitted to the hospital for voluntary sterilization by laparoscopic technique, were randomly allocated to a control or one of two treatment groups. Treatments were given with either a single dose of 200 mg mifepristone or 0.75 mg levonorgestrel in two doses 12 h apart, on day LH+2. Surgery was performed on day LH+4 to LH+6. Steroid receptor expression was analysed by immunohistochemistry, Western blot and RT-PCR. In the controls, there was a higher concentration of progesterone receptors in the stromal cells in the isthmic region than in those in the ampullar region. Treatment with mifepristone increased the progesterone receptor concentration in epithelial and stromal cells and increased the estrogen receptor concentration in epithelial cells. No effect on steroid receptor concentration was found following levonorgestrel. The contraceptive effect of post-ovulatory mifepristone has previously been considered to be dependent on an effect on the endometrium. However an effect on the Fallopian tube could contribute to alter the peri-implantation milieu influencing fertilization and embryo development.

Tibolone seems to have little influence on breast cell proliferation.

No abstract

Insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin are recognized as crucial signals for the initiation and maintainance of decidualization. The purpose of the study was to investigate the effect of mifepristone on the expression of IGFBP-1, prolactin and progesterone receptors (PR) during the implantation phase in human endometrium. Eight fertile women were studied during control and treatment cycles. Treatment with 200 mg of mifepristone was administered on day LH +2. Endometrial samples were collected on day LH +6 to +8. Expression of IGFBP-1, prolactin and PR was identified using immunohistochemistry, and mRNA levels were determined with RT-PCR. In control specimens, IGFBP-1 and prolactin were localized to the cytoplasm of the endometrial glandular and to a lesser extent in stromal cells. In the same samples, PR immunoreactivity was detected in the nucleus of the endometrial stromal cells, and was absent from the glandular cells. After mifepristone treatment, there was a significant increase in the immunostaining and mRNA expression for IGFBP-1 and PR. Prolactin expression increased only slightly after treatment. These results support the view that administration of mifepristone in the early luteal phase does not simply retard endometrial development. Our findings provide further insight into the regulation of IGFBP-1 and prolactin by PR in the human endometrium in vivo.