| Abstract | Although estrogen replacement has been the main therapy to prevent and treat osteoporosis, there are concerns about its safety. Phytoestrogens have attracted attention to their potential impacts in osteoporosis prevention and treatment. Among phytoestrogens, the isoflavone daidzein (Dz) acts on transcription via the intracellular estrogen receptors (ER), mainly ERbeta, in osteoblasts, but mimics only part of the estrogen effects. Since estradiol also exerts rapid effects in osteoblasts, we investigated the multistep processes involved in the rapid actions of low (1-100 pM) doses of daidzein. Dz bound to a membrane moiety, related to ERbeta since the calcium response to Dz was blocked by an anti-ERbeta antibody directed against the C-terminus, but not by a double-stranded siRNA specific for ERbeta. This protein was coupled to a pertussis toxin (PTX)-sensitive Gbeta1 subunit whose transducer was PLC-beta2, which triggered a rapid (5 sec) mobilization of calcium from the endoplasmic reticulum. Dz phosphorylated within 15 sec ERK1/2 whose phosphorylation involved two routes: Gbeta1/PLC-beta2/PKC/c-Raf-1/MEK1/2 and Gbeta1/PI3K/cSrc/c-Raf-1/MEK1/2 as shown using several inhibitors. Dz induced rapid (1 min) changes in the actin cytoskeleton via the two routes. The rapid (20 sec) phosphorylation of Elk-1 and CREB by Dz involved Gbeta1 and ERK1/2. All the processes were insensitive to the estradiol antagonist ICI 182,780. In conclusion, the rapid effects of Dz seem to be biologically relevant for the function of osteoblast in bone since the isoflavone activates transcription factors linked to early genes controlling cellular proliferation and differentiation, and modulates actin cytoskeleton which controls cell adhesion, division, or secretion. |
| Authors | Anne de Wilde, Christine Heberden, Gilles Chaumaz, Christian Bordat, Michele Lieberherr
(Affiliation: The Institut National de la Recherche Agronomique, Laboratoire de Nutrition et de Santé Alimentaire, 78350 Jouy-en-Josas, France.)
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| Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 209
Issue 3
Pg. 786-801
(Dec 2006)
ISSN: 0021-9541 United States |
| PMID | 16972265
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Copyright | (c) 2006 Wiley-Liss, Inc. |
| Chemical References |
- Actins
- Estrogen Receptor beta
- Estrogens
- GTP-Binding Protein beta Subunits
- Isoenzymes
- Isoflavones
- Phytoestrogens
- Transcription Factors
- daidzein
- Calcium
- Extracellular Signal-Regulated MAP Kinases
- Protein Kinase C
- Type C Phospholipases
|
| Topics |
- Actins
(metabolism)
- Animals
- Calcium
(metabolism)
- Cell Membrane
(metabolism)
- Cytoskeleton
(metabolism)
- Estrogen Receptor beta
(genetics, metabolism)
- Estrogens
(metabolism)
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Female
- GTP-Binding Protein beta Subunits
(genetics, metabolism)
- Isoenzymes
(metabolism)
- Isoflavones
(pharmacology)
- Osteoblasts
(cytology, drug effects, metabolism)
- Phytoestrogens
(pharmacology)
- Protein Kinase C
(metabolism)
- Rats
- Rats, Wistar
- Signal Transduction
(physiology)
- Transcription Factors
(metabolism)
- Type C Phospholipases
(metabolism)
|
