receptor mediating its action as in the progesterone-induced reinitiation of meiosis in Xenopus laevis oocytes (Blondeau and Baulieu, 1985). However, in sperm, as well as in oocytes, RU 486 may not act as an antiprogestin at the membrane-receptor level. A preliminary report (C.G.P. Puri, patent preview WO 9210194A1, 1992) of a contraceptive effect of RU 486 in monkeys with a decrease of sperm counts has not, to my current knowledge, yet been confirmed.
RU 486 can suppress ovulation, and inhibit the mitotic action of estrogens in the monkey endometrium. These effects suggest that the compound may be useful for the treatment of endometriosis (Kettel et al., 1991). As expected, in women, RU 486 suppressed ovulation and menstrual cycle, and brought about an increase of LH (with augmented pulse amplitude but not frequency), adrenocorticotropic hormone (ACTH), and cortisol. Pain was decreased, but there was no decrease in the extent of the disease (corroborating observations in the rat by Tjaden et al., 1993); an effect on lipid peroxidation has also been described (Morales et al., 1992).
Murphy and coworkers (1993) have reported a 50 percent regression of uterine leiomyomas by daily administration of 50 mg of RU 486 for several weeks. This may be due principally to induced anovulation. Modulation of uterine growth factors and insulin-like growth factor (IGF)-binding proteins may also be involved (Murphy et al., 1993).
The treatment provokes an increase of LH, but not of FSH, and of dehydroepiandrosterone sulfate, androstenedione, testosterone, and cortisol, while estrogens, progesterone, sex steroid-binding plasma protein (SBP), thyroid-stimulating hormone (TSH), and prolactin (PRL) are unchanged, compared to original early follicular phase levels. In myometrial and leiomyomatous tissue, PR but not ER immunoreactivity is decreased. Amenorrhea and anovulation are constant. The significant decrease of PR levels may indicate a direct antiprogesterone effect; however, an alteration in ER function cannot be excluded, as discussed above.
The human papillomavirus (type 16, episomal) expression in ectocervical cells (cervical keratinocytes) is stimulated by glucocorticosteroids and progesterone (Mittal et al., 1993). Since RU 486 may inhibit this