Vascular ECE-1 mRNA expression decreases in response to estrogens.
DNA microarrays were used to identify new targets of estrogen in the vasculature. Ovariectomized rats were treated with estradiol, genistein or daidzein, for four days. [33P]dCTP-labelled probes synthesized from mesenteric artery RNA were hybridized with DNA microarrays. Analysis of the microarray data identified endothelin converting enzyme-1 (ECE-1) as a gene whose expression was inhibited by treatment with estrogen, genistein, or daidzein. Semi-quantitative RT-PCR was used to confirm the data from the DNA microarrays. Reversal of the estrogen and phytoestrogen effect on ECE-1 expression by ICI 182,780 suggested that the inhibition was an estrogen receptor response. An inhibition of ECE-1 mRNA expression by estrogen or the phytoestrogens has not been previously reported. These data highlight the power of DNA microarray technology to identify new gene expression targets of estrogen in the vasculature. Moreover, the data suggest that genistein and daidzein inhibit ECE-1 expression by an estrogen receptor-mediated mechanism.
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D004359:Drug Therapy, Combination; D000072396:Endothelin-Converting Enzymes; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D020869:Gene Expression Profiling; D019833:Genistein / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects*; D008666:Metalloendopeptidases; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004967:Estrogens; D007529:Isoflavones; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; C004742:daidzein; D019833:Genistein; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes