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Related Experiment Videos

Vascular ECE-1 mRNA expression decreases in response to estrogens.

Manoj C Rodrigo1, Douglas S Martin, Kathleen M Eyster

  • 1Hypertension Unit, Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, 414 E Clark St, Vermillion, SD 57069, USA.

Life Sciences
|October 2, 2003
PubMed
Summary

Estrogen and phytoestrogens like genistein inhibit endothelin converting enzyme-1 (ECE-1) expression in the vasculature. This estrogen receptor-mediated effect on ECE-1 was identified using DNA microarrays.

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Area of Science:

  • Vascular biology
  • Endocrinology
  • Molecular biology

Background:

  • Estrogen plays a crucial role in vascular health.
  • Phytoestrogens, such as genistein and daidzein, are plant-derived compounds with estrogen-like activity.
  • Identifying novel estrogen targets in the vasculature is important for understanding cardiovascular regulation.

Purpose of the Study:

  • To identify new molecular targets of estrogen action in the vasculature using DNA microarray technology.
  • To investigate the effect of estradiol, genistein, and daidzein on gene expression in the rat mesenteric artery.
  • To determine if the observed effects are mediated through the estrogen receptor.

Main Methods:

  • DNA microarrays were employed to analyze gene expression profiles in mesenteric artery RNA from ovariectomized rats treated with estradiol, genistein, or daidzein.

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  • Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to validate microarray findings.
  • The role of the estrogen receptor was assessed using ICI 182,780, an estrogen receptor antagonist.

    • Main Results:

    • DNA microarray analysis identified endothelin converting enzyme-1 (ECE-1) as a significantly downregulated gene following treatment with estrogen, genistein, or daidzein.
    • RT-PCR confirmed the inhibition of ECE-1 mRNA expression by these compounds.
    • The inhibitory effect of estrogen and phytoestrogens on ECE-1 expression was reversed by ICI 182,780, indicating an estrogen receptor-dependent mechanism.

    Conclusions:

    • DNA microarray technology is a powerful tool for discovering novel vascular targets of estrogen.
    • Estrogen and phytoestrogens (genistein, daidzein) inhibit ECE-1 expression in the vasculature.
    • The inhibition of ECE-1 by genistein and daidzein occurs via an estrogen receptor-mediated pathway, a finding not previously reported.