Estrogen-induced cell signaling in the sexually dimorphic nucleus of the rat preoptic area: potential involvement of cofilin in actin dynamics for cell migration

Biochem Biophys Res Commun. 2013 May 3;434(2):287-92. doi: 10.1016/j.bbrc.2013.02.117. Epub 2013 Mar 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Movement*
  • Cofilin 1 / genetics
  • Cofilin 1 / metabolism*
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase 5 / metabolism
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / metabolism
  • Estradiol / pharmacology*
  • Female
  • Immunohistochemistry
  • Lim Kinases / genetics
  • Lim Kinases / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Pregnancy
  • Preoptic Area / drug effects*
  • Preoptic Area / embryology
  • Preoptic Area / metabolism
  • Protein Kinase C-delta / genetics
  • Protein Kinase C-delta / metabolism
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Signal Transduction
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Actins
  • Cfl1 protein, rat
  • Cofilin 1
  • Estradiol
  • Prkcd protein, rat
  • Cyclin-Dependent Kinase 5
  • Lim Kinases
  • Limk1 protein, rat
  • Pak1 protein, rat
  • p21-Activated Kinases
  • Protein Kinase C-delta
  • Cdk5 protein, rat
  • Rac1 protein, rat
  • rac1 GTP-Binding Protein