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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis

H Watanabe1, E Takahashi, M Kobayashi

  • 1Okazaki Institute for Integrative Bioscience, National Institutes of Natural Science, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan.

Journal of Molecular Endocrinology
|February 8, 2006
PubMed

Insights

Estrogen directly activates the adrenomedullin (ADM) gene in the uterus, influencing uterine growth. This estrogen-induced ADM expression in the uterine stroma contributes to broader biological effects.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Genomics

Background:

  • Estrogen influences hundreds of uterine genes, but direct regulation mechanisms remain unclear.
  • Understanding estrogen's direct targets is crucial for deciphering uterine physiology.

Purpose of the Study:

  • To identify genes directly regulated by estrogen in the uterus.
  • To investigate the role of adrenomedullin (ADM) in estrogen-mediated uterine responses.

Main Methods:

  • Mice were treated with varying estrogen doses to observe gene expression patterns.
  • Dose-response expression analysis was correlated with uterine growth.
  • Chromatin immunoprecipitation (ChIP) assays were used to confirm estrogen receptor binding.
  • Gene expression was analyzed in estrogen receptor-alpha-null mice.

Main Results:

  • Estrogen directly upregulates the adrenomedullin (ADM) gene in a dose-dependent manner, mirroring uterine growth.
  • ADM expression is induced early and localized to the endometrial stroma.
  • Estrogen receptor binds directly to the ADM promoter and RAMP3 intron.
  • ADM and RAMP3 gene activation is dependent on estrogen receptor-alpha.

Conclusions:

  • Estrogen directly regulates ADM gene expression in the uterine stroma.
  • Spatiotemporally regulated ADM expression contributes to diverse biological effects beyond myometrial expression.
  • This study elucidates a novel mechanism of estrogen action in the uterus.

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