Abstract
Estrogen is a key factor to induce the sexually dimorphic nucleus (SDN) in the preoptic area (POA) of the rat brain. Identification of estrogen-dependent signaling pathways at SDN in POA during the critical period is a prerequisite for elucidating the mechanism. In the present study, we treated female rats with/without 17β-estradiol (E2) at birth, designated as postnatal day 1 (P1), and prepared total RNA from brain slices containing SDN for DNA microarray analysis. Among the estrogen-responsive genes identified, protein kinase C-delta (PKC-δ) was significantly up-regulated by E2 at P5. We examined the downstream effectors of PKC-δ protein by Western blotting and found an E2-induced PKC-δ/Rac1/PAK1/LIMK1/cofilin pathway. In the pathway, E2 suppressed the phosphorylation (inactive form) of cofilin. This result was supported by immunohistochemistry, where the phosphorylation/dephosphorylation of cofilin occurred at SDN, which suggests that cell migration is a cue to create sexual dimorphism in POA.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism*
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Animals
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Animals, Newborn
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Blotting, Western
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Cell Movement*
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Cofilin 1 / genetics
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Cofilin 1 / metabolism*
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Cyclin-Dependent Kinase 5 / genetics
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Cyclin-Dependent Kinase 5 / metabolism
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Embryo, Mammalian / drug effects
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Embryo, Mammalian / metabolism
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Estradiol / pharmacology*
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Female
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Immunohistochemistry
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Lim Kinases / genetics
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Lim Kinases / metabolism
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Oligonucleotide Array Sequence Analysis
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Phosphorylation
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Pregnancy
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Preoptic Area / drug effects*
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Preoptic Area / embryology
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Preoptic Area / metabolism
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Protein Kinase C-delta / genetics
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Protein Kinase C-delta / metabolism
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Rats
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Rats, Wistar
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Sex Characteristics*
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Signal Transduction
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p21-Activated Kinases / genetics
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p21-Activated Kinases / metabolism
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism
Substances
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Actins
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Cfl1 protein, rat
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Cofilin 1
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Estradiol
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Prkcd protein, rat
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Cyclin-Dependent Kinase 5
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Lim Kinases
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Limk1 protein, rat
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Pak1 protein, rat
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p21-Activated Kinases
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Protein Kinase C-delta
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Cdk5 protein, rat
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Rac1 protein, rat
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rac1 GTP-Binding Protein