Biological Responses of Antiprogestins in Mammary Gland, Uterus and Seminal Vesicles of Prepubertal Intact and Adult Gonadectomized Mice

Abstract

The present study tested and compared the antiproliferative and proliferative activities of three antiprogestins on four separate mouse model systems: prepubertal intact and adult ovariectomized (OVX) females, prepubertal intact and adult castrated males. In prepubertal intact males and females and adult castrated males, norethindrone acetate (NA; a synthetic steroid exhibiting progestational and estrogenic activities)- stimulated mammary growth was decreased by antiprogestins: more by RU 46556 (RU) than RU 38486 (MI) and onapristone (ON). In adult OVX females the inhibitory effect of RU and MI was lower than that of ON. Uterine weights were not significantly decreased by MI, were significantly decreased by RU at a lower daily dose (50 μg) but not affected by a high (500 μg) dose. Seminal vesicle weights were increased by RU but not affected by MI in both NA-treated prepubertal and adult castrated males. In adult castrated but not in prepubertal males ON decreased seminal vesicle weights. In 17β-estradiol (E) plus progesterone (Prog)-treated animals of all four model systems, RU (100 μg/d) acted additively with a submaximal daily dose (10 μg) of antiestrogen ICI 182, 780 (ICI) to produce a lower mammary gland growth rate than ICI alone. In uterus, however, no significant effect of a combination of ICI plus RU was noted when compared with ICI alone. In general, our assay could serve as an in vivo tool for the detection of steroid hormone agonist and antagonist activities of newly synthesized analogs of steroid hormones, and natural and man-made chemicals and extracts of environmental samples.