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Tissue-specific modulation of cyclooxygenase-2 (Cox-2) expression in the uterus and the v. cava by estrogens and phytoestrogens.
Tissue-specific modulation of cyclooxygenase-2 (Cox-2) expression in the uterus and the v. cava by estrogens and phytoestrogens.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 2005 Nov 24; Vol. 243 (1-2), pp. 51-7. Date of Electronic Publication: 2005 Nov 04. - Publication Year :
- 2005
-
Abstract
- Cyclooxygenase 2 (Cox-2), an enzyme involved in prostaglandin production, is a key player in the development of pathologic changes, such as colorectal cancer, arteriosclerosis and thrombosis. In this study, we investigated the effects of estrogens, selective estrogen receptor modulators (SERMs), pure antiestrogens and phytoestrogens on the tissue-specific expression of Cox-2 in the uterus and the v. cava of ovariectomized female rats. Cox-2 expression could be detected in the uterine epithelium and in the endothelium of the v. cava. Cox-2 expression was time-dependently stimulated after administration of 17beta estradiol (E2) in the uterus. In the v. cava, E2 treatment resulted in a stimulated expression of the progesterone receptor (PR), a gene known to be regulated by E2, whereas Cox-2 was simultaneously down-regulated. Administration of the pure antiestrogen faslodex (Fas) had no effect on Cox-2 expression. In contrast, administration of tamoxifen (Tam) resulted in a decrease of Cox-2 expression in the v. cava but does not stimulate Cox-2 expression in the uterus. Interestingly, the same expression pattern of Cox-2 could be detected after dose-dependent administration of genistein (Gen). Here, down-regulation of Cox-2 could already be detected after administration of merely 0.5 mg/(kgBW) Gen, a dose where no effects on uterine weight were observed. In summary, our results demonstrate a reverse tissue-specific regulation of Cox-2 expression by estrogens in the v. cava and uterus indicating the existence of complex molecular mechanisms which have to be characterized in future studies. Remarkably, Tam and the phytoestrogen Gen, both share the ability to decrease the expression of Cox-2 in the v. cava without effecting its uterine expression. These observations may be of great importance with respect to potential beneficial or adverse effects of estrogens, SERMs and phytoestrogens on the cardiovascular tissue.
- Subjects :
- Animals
Cyclooxygenase 2 genetics
Estradiol analogs & derivatives
Estradiol pharmacology
Female
Fulvestrant
Gene Expression Regulation, Enzymologic
Genistein pharmacology
Phytoestrogens pharmacology
Rats
Rats, Wistar
Receptors, Progesterone metabolism
Selective Estrogen Receptor Modulators pharmacology
Tamoxifen pharmacology
Uterus enzymology
Venae Cavae enzymology
Cyclooxygenase 2 biosynthesis
Estrogens pharmacology
Uterus drug effects
Venae Cavae drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0303-7207
- Volume :
- 243
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 16274925
- Full Text :
- https://doi.org/10.1016/j.mce.2005.08.007