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 (E 2 ) 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 E 2 at P5. We examined the downstream effectors of PKC-δ protein by Western blotting and found an E 2 -induced PKC-δ/Rac1/PAK1/LIMK1/cofilin pathway. In the pathway, E 2 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.