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. Author manuscript; available in PMC: 2013 Dec 13.
Published in final edited form as: Brain Res. 2012 Dec 19;1514:63–74. doi: 10.1016/j.brainres.2012.12.015

Figure 5. Summary of Estrogen Regulation of Dkk1 and Wnt/β-Catenin Signaling.

Figure 5

This figure depicts three currently proposed mechanisms for 17β-estradiol’s regulation of Dkk1 and Wnt/β-Catenin signaling in the brain. 1) E2 can suppress expression of the neurodegenerative Wnt antagonist Dkk1 in the hippocampus, particularly following an ischemic insult. 2) E2 can enhance canonical Wnt signaling in the hippocampus, particularly following an ischemic insult, through induction of Wnt3, which leads to expression of pro-survival Wnt target genes, such as Survivin, through β-Catenin and TCF. 3) E2, either acting alone or in concert with IGF-1, can initiate a membrane receptor-mediated PI3K/Akt/GSK3β signaling cascade, which leads to the stabilization of cytosolic β-Catenin and Wnt-independent gene expression through β-Catenin and LEF-1. Akt, A Serine/Threonine Kinase (also known as Protein Kinase B); β-Cat, Beta-Catenin; CKI, Casein Kinase 1; Dkk1, Dickkopf-1; Dvl, Disheveled; E2, 17β-Estradiol; ER, Estrogen Receptor; GSK3β, Glycogen Synthase Kinase 3 Beta; IGF-I, Insulin-like Growth Factor-1; IGF-IR, Insulin-like Growth Factor-1 Receptor; IRS-1, Insulin Receptor Substrate 1; LEF-1, Lymphoid Enhancing Factor 1; LRP 5/6, Low-Density Lipoprotein 5/6; PI3K, Phosphatidylinositol 3 Kinase; TCF, T Cell Factor; Wnt, Wingless.