Estradiol signaling via sequestrable surface receptors.
Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway.
Division of Molecular Parasitology and Centre of Biological-Medical Research, Heinrich-Heine-University, 40225 Duesseldorf, Germany.
W P
WP
Benten
C
C
Stephan
M
M
Lieberherr
F
F
Wunderlich
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology*; D011959:Receptors, Estradiol / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011959:Receptors, Estradiol; D012710:Serum Albumin, Bovine; D004958:Estradiol; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium