Effects of chronic genistein treatment in mammary gland, uterus, and vagina.
BACKGROUND
The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy.


OBJECTIVE
We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17beta-estradiol [E(2); 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland.


RESULTS
In rats treated with either of the E(2) doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E(2) dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E(2) (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E(2) (both doses) but not by GEN.


CONCLUSIONS
In summary, E(2) and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit.
Rimoldi
Guillermo
G
Department of Clinical and Experimental Endocrinology, Georg-August-University, Göttingen, Germany.
Christoffel
Julie
J
Seidlova-Wuttke
Dana
D
Jarry
Hubertus
H
Wuttke
Wolfgang
W
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism
D007529:Isoflavones; D048789:Phytoestrogens; D018809:Proliferating Cell Nuclear Antigen; D011980:Receptors, Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D019833:Genistein