title: In vivo imaging of transcriptionally active estrogen receptors.
abstract: Through intracellular receptors, estrogens control growth, differentiation and function of not only reproductive tissues, but also other systems. 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 neurotransmitters. To determine the dynamics of estrogen receptor activity and the dependence of estrogen receptor on 17beta-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.
authors.affiliation: Centre of Excellence on Neurodegenerative Diseases and Institute of Pharmacological Sciences, Milan University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
authors.forename: Michele
authors.initials: M
authors.lastname: Raviscioni
authors.forename: Paola
authors.initials: P
authors.lastname: Mussi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vegeto
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Parker
authors.forename: Clemens
authors.initials: C
authors.lastname: Lowik
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D004958:Estradiol / Q000378:metabolism*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D004958:Estradiol; D008156:Luciferases