The differential ability of the phytoestrogen genistein and of estradiol to induce uterine weight and proliferation in the rat is associated with a substance specific modulation of uterine gene expression.
In this study the ability of the phytoestrogen genistein (GEN) to regulate proliferation in the rat uterine tissue and the associated molecular mechanisms were investigated in a dose and time dependent manner. A single administration of GEN induced a rapid increase of the uterine weight during the first 24 h. In contrast to E2, treatment with GEN for 3 days did not result in a further increase of the uterine weight. GEN only marginally effected the thickness of the uterine epithelium and the expression of epithelial proliferating cell nuclear antigen (PCNA). Whereas, estrogen sensitive genes were modulated significantly, the expression of key genes involved in the regulation of proliferation (PCNA, ERalpha /ERbeta ratio) remained unaffected by GEN. Our results indicate that GEN has only a limited ability to activate molecular mechanisms involved in the induction of proliferation whereas estrogen sensitive genes are induced in a estrogen like manner.
Diel
Patrick
P
Department Molecular and Cellular Sports Medicine, DSHS Cologne, Carl Diem Weg 6, 50927 Köln, Germany. diel@dshs-koeln.de
Geis
Renate-B
RB
Caldarelli
Antonio
A
Schmidt
Simone
S
Leschowsky
Ute Laudenbach
UL
Voss
Anika
A
Vollmer
Günter
G
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000032:analysis / Q000235:genetics; D014599:Uterus / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D048789:Phytoestrogens; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011987:Receptors, Steroid; D004958:Estradiol; D019833:Genistein