Estradiol signaling via sequestrable surface receptors

Endocrinology. 2001 Apr;142(4):1669-77. doi: 10.1210/endo.142.4.8094.

Abstract

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.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Estradiol / metabolism
  • Estradiol / physiology*
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate
  • Macrophages / metabolism
  • Mice
  • Microscopy, Confocal
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / physiology*
  • Receptors, Estradiol / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin, Bovine / metabolism
  • Signal Transduction / physiology*

Substances

  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Estradiol
  • Serum Albumin, Bovine
  • Estradiol
  • Fluorescein-5-isothiocyanate
  • Calcium