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In vivo imaging of transcriptionally active estrogen receptors

Nature Medicine volume 9, pages 82–86 (2003)Cite this article

Abstract

Through intracellular receptors, estrogens control growth, differentiation and function of not only reproductive tissues, but also other systems1,2,3. Estrogen receptors are ligand-dependent transcription factors whose activity is modulated either by estrogens, or by alternative intracellular signaling pathways downstream of growth factors and neurotransmitters4,5,6. To determine the dynamics of estrogen receptor activity and the dependence of estrogen receptor on 17β-estradiol in vivo, we generated a transgenic mouse that expresses a luciferase reporter gene under the control of activated estrogen receptors. As expected, luciferase activity, monitored with a cooled charged coupled device camera, paralleled circulating estrogen levels in reproductive tissues and in liver, indicating that the peak transcriptional activity of the estrogen receptor occurred at proestrus. In contrast, in tissues such as bone and brain, the peak activity of estrogen receptors was observed at diestrus. These tissue-specific responses are masked when mice undergo conventional hormone treatment. We also demonstrate that estrogen receptors are active in immature mice before gonadal production of sex hormones as well as in ovariectomized adult mice. These findings emphasize the importance of hormone-independent activation of the estrogen receptor, and have implications for the therapeutic use of estrogens, such as hormone replacement therapy.

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Figure 1: ER activation during the estrous cycle.
Figure 2: Effect of administration of exogenous 17β-estradiol on ER activity.
Figure 3: ER transcriptional activity in immature and adult mice.

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Acknowledgements

We thank P. Chambon for extended discussion; J.Å. Gustafsson, B. Katzenellenbogen, S. Tsai and K. Yamamoto for critical reading of the manuscript; and M. Rebecchi and C. Meda for technical assistance. The present study was supported by Italian Association for Cancer Research, Italian Ministry for Education, CARIPLO, Telethon (E 600), European Community QLRT-2001-02221.

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Authors and Affiliations

  1. Centre of Excellence on Neurodegenerative Diseases and Institute of Pharmacological Sciences, Milan University, Milan, Italy

    Paolo Ciana, Michele Raviscioni, Paola Mussi, Elisabetta Vegeto & Adriana Maggi

  2. Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

    Ivo Que & Clemens Lowik

  3. Institute of Reproductive and Developmental Biology, Hammersmith Hospital, ICSM, London, UK

    Malcolm G. Parker

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  1. Paolo Ciana
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Correspondence to Adriana Maggi.

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Ciana, P., Raviscioni, M., Mussi, P. et al. In vivo imaging of transcriptionally active estrogen receptors. Nat Med 9, 82–86 (2003). https://doi.org/10.1038/nm809

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