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The non-genomic Action of Sex Steroids

  • Joe I 
  • Kipp J L 
  • Ramirez V D 
Conference paper
Part of the Research and Perspectives in Endocrine Interactions book series (RPEI)

Summary

The aim of this paper is to discuss novel and rather recent evidence indicating that estradiol and testosterone have rapid actions by interacting with two different, but physiologically and chemically well-characterized proteins: 1) tubulin, a basic component of microtubules and therefore involved in cellular cytoarchitecture and cellular trafficking; and 2) glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme involved in glycolysis but also in other important, non-glycolytic functions.

Estradiol and testosterone bind to tubulin at nanomolar concentrations and exert opposite effects on microtubule polymerization in an in vitro assay that uses electron microscopy to visualize the formation of microtubules: estradiol disrupts polymerization whereas testosterone stabilizes microtubules. This finding was confirmed by spectrometric analysis and in vivo cell cultures using image visualization of tubulin. Interestingly, testosterone but not estradiol blocks the colchicine-induced depolymerization effect in both the pure tubulin assay and the cell culture model.

Previously, we reported that estradiol binds with high affinity and selectivity to GAPDH and that a single injection of estradiol (10 µg, s.c.) to ovariectomized rats significantly increased and recovered the reduced catalysis of the enzyme in the plasmalemma-microsomal fraction (P3 fraction) of the hippocampus of these rats to intact levels. Herein, we report that estradiol induces a rapid (within 30 min) translocation of the enzyme to the P3 fraction of primary hippocampus cell cultures as well in the hippocampal cell line (HT-22) that lacks functional alfa and beta estrogen receptors. Importantly, the translocation is accompanied by serine phosphorylation of the GAPDH as shown by Western blot analysis of the P3 fraction. Estradiol treatment (10 nM) of HT-22 cell cultures appears to sequester the GAPDH in membrane organelles visualized by immunocytochemistry, because they become resistant to depletion by the nonionic detergent Triton-X-100.

These results and related reports from other laboratories cited in this paper strongly support the concept that, by interacting with these two proteins and other cellular components, sex steroids are involved in rapid, non-genomic functions in a variety of cells.

Keywords

Okadaic Acid Microtubule Dynamic Microtubule Polymerization Beta Estrogen Receptor Medial Basal Hypothalamus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Joe I 
    • 1
  • Kipp J L 
    • 1
  • Ramirez V D 
    • 1
  1. 1.Department of Molecular and Integrative PhysiologyUniversity of Illinois at UrbanaUSA

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