Effects of various phytoestrogens and of Cimicifuga racemosa (CR) in the mammary gland of ovariectomized (ovx) rats

Soy and red clover extracts or thereof purified isoflavones (genistein, daidzein and its metabolite equol) are known to be estrogenic in the uterus but their effects in the mammary gland are unknown. The CR extract BNO 1055 (CR) has no estrogenic effect. An action in the mammary gland was not yet studied. Therefore, we treated ovx rats orally with genistein (15.5mg/day), daidzein (15.8mg/day) and equol (15.8mg/day) and with CR (30.0mg/day) for a period of 3 months. Control ovx animals received soy free or estradiol 17ß (E2) containing food (0.25mg/day).

Mammary glands were morphometrically analyzed and the proliferative activity tested by counting cells stained with an antibody against proliferating cell nuclear antigen (PCNA). Uteri were collected and weighed. The mammary glands of negative control animals were atrophic and consisted mostly of lobuli type II (less than 5 alveoli per lobulus). E2 treatment stimulated the number of lobuli type I and type II (more than 5 alveoli per tubulus, p<0.001) and secretory material was present. Genistein > daidzein > equol but not CR stimulated the number of lobuli type I and type II (p<0.001). The numbers of PCNA expressing cells were increased in the same magnitude. The E2 treated animals had largest uteri and genistein, daidzein but not equol stimulated uteri weights whereas no such estrogenic effect was seen in the uteri in the CR treated animals.

It is concluded that genistein > daidzein > equol have not only uterotropic but also significant mammatropic effects whereas CR is devoid of such estrogenic effects in the uterus and the mammary gland.