Morphologic changes induced by oral long-term treatment with 8-prenylnaringenin in the uterus, vagina, and mammary gland of castrated rats

Abstract

Objective: The flavonoid 8-prenylnaringenin (8-PN) is found in hops, and hence in beer, and is also increasingly consumed as a food supplement. It is the strongest known phytoestrogen, which makes it a good candidate as an alternative to hormone therapy. Its putatively undesired estrogenic effects in the uterus and mammary gland have not yet been thoroughly investigated. Therefore, we performed a long-term oral administration experiment. Design: Rats were ovariectomized and fed for 3 months with soy-free chow containing estradiol (E2) or 8-PN, both in two doses (8-PN: 6.77 mg or 68.42 mg/kg body weight; E2: 0.17 mg or 0.7 mg/kg body weight) or no additives. Analysis was mainly focused on morphologic and immunocytochemical parameters. Expression of proliferating cell nuclear antigen as a proliferation marker and of progesterone receptor was quantified in the mammary gland. Results: Uteri of animals treated with both E2 doses and the high 8-PN dose had increased weight and showed histologic estrogen-induced features. 8-PN at the high dose induced epithelial polypoid formation unique to this group. Compared to the atrophic controls, both E2 doses and the high 8-PN dose induced hyperplastic epithelia in the vagina. The high doses of E2 and 8-PN caused secretion in the mammary gland, whereas proliferation and progesterone receptor expression were stimulated by both E2 doses and the high 8-PN dose. Conclusions: E2 and 8-PN share many effects in the three studied organs, but some differences in the mechanism of action appear to exist.