title: Estrogen-induced cell signaling in the sexually dimorphic nucleus of the rat preoptic area: potential involvement of cofilin in actin dynamics for cell migration.
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.
authors.affiliation: Department of Physiology, Nippon Medical School, Tokyo 113-8602, Japan. ywkiyama@nms.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wada-Kiyama
authors.forename: Chiaki
authors.initials: C
authors.lastname: Suzuki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Dilip
authors.initials: D
authors.lastname: Rai
authors.forename: Ryoiti
authors.initials: R
authors.lastname: Kiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakuma
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011247:Pregnancy; D011301:Preoptic Area / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C495812:Cfl1 protein, rat; D051338:Cofilin 1; D004958:Estradiol; C497260:Prkcd protein, rat; D051360:Cyclin-Dependent Kinase 5; D054461:Lim Kinases; C515894:Limk1 protein, rat; C515906:Pak1 protein, rat; D054462:p21-Activated Kinases; D051745:Protein Kinase C-delta; C495907:Cdk5 protein, rat; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein