Reduction of post injury neointima formation due to 17beta-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182,780 in vitro.
BACKGROUND
Animal and organ culture experiments have shown beneficial inhibitory estrogen effects on post injury neointima development. The purpose of this study was to investigate whether such estrogen effects are influenced by the estrogen receptor antagonist ICI 182,780. Different concentrations of 17beta-estradiol and the phytoestrogens genistein and daidzein were tested.


METHODS
Female New Zealand White rabbits were benumbed. In situ vascular injury of the thoracic and abdominal aorta was performed by a 3F Fogarty catheter. Segments of 5 mm were randomised and held in culture for 21 days. Three test series were performed: 1) control group--20 microM ICI--30 microM ICI--40 microM ICI. 2) control group--20 microM ICI--40 microM 17beta-estradiol--40 microM 17beta-estradiol + 20 microM ICI. 3) control group--20 microM ICI--40 microM daidzein--40 microM daidzein + 20 microM ICI--20 microM genistein--20 microM genistein + 20 microM ICI. After 21 days the neointima-media-ratio was evaluated.


RESULTS
1) Treatment with ICI 182,780 did not reduce neointima formation significantly (p = 0.05). 2) 40 microM 17beta-estradiol alone (p < 0.0001) and in combination with 20 microM ICI (p < 0.0001) reduced neointima formation significantly. 3) 20 microM genistein alone (p = 0.0083) and combined with 20 microM ICI (p = 0.0053) reduced neointima formation significantly. 40 microM daidzein did not have a significant (p = 0.0637) effect.


CONCLUSIONS
The estrogen receptor antagonist ICI 182,780 did not modulate the inhibitory estrogen effects on post injury neointima formation. These results do not support the idea that such effects are mediated by vascular estrogen receptors.
Finking
Gerald
G
Institute of Occupational, Social, and Environmental Medicine, University of Ulm, Ulm, Germany. gerald.finking@medizin.uni-ulm.de
Lenz
Christina
C
Schochat
Thomas
T
Hanke
Hartmut
H
D000818:Animals; D001011:Aorta; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D048789:Phytoestrogens; D028321:Plant Preparations / Q000494:pharmacology; D011651:Pulmonary Artery; D011817:Rabbits; D011897:Random Allocation; D017539:Tunica Intima / Q000187:drug effects* / Q000254:growth & development / Q000293:injuries
D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D000077267:Fulvestrant; D004958:Estradiol; C004742:daidzein; D019833:Genistein