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


METHODS
Rats were ovariectomized and fed for 3 months with soy-free chow containing estradiol (E(2)) or 8-PN, both in two doses (8-PN: 6.77 mg or 68.42 mg/kg body weight; E(2): 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 E(2) 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 E(2) doses and the high 8-PN dose induced hyperplastic epithelia in the vagina. The high doses of E(2) and 8-PN caused secretion in the mammary gland, whereas proliferation and progesterone receptor expression were stimulated by both E(2) doses and the high 8-PN dose.


CONCLUSIONS
E(2) and 8-PN share many effects in the three studied organs, but some differences in the mechanism of action appear to exist.
Rimoldi
Guillermo
G
Department of Clinical and Experimental Endocrinology, University of Göttingen, Göttingen, Germany.
Christoffel
Julie
J
Wuttke
Wolfgang
W
D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology*; D027582:Humulus; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D008593:Menopause; D010052:Ovariectomy; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology
C119737:8-prenylnaringenin; D044950:Flavanones; D048789:Phytoestrogens