In vivo imaging of transcriptionally active estrogen receptors.
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.
Ciana
Paolo
P
Centre of Excellence on Neurodegenerative Diseases and Institute of Pharmacological Sciences, Milan University, Milan, Italy.
Raviscioni
Michele
M
Mussi
Paola
P
Vegeto
Elisabetta
E
Que
Ivo
I
Parker
Malcolm G
MG
Lowik
Clemens
C
Maggi
Adriana
A
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
D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D004958:Estradiol; D008156:Luciferases