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. 2018 Jul 5;8:10212. doi: 10.1038/s41598-018-28395-w

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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EE2 and LNG affected the phosphorylation of proteins involved in brain development, synaptic plasticity, neurogenesis, synaptic transmission, and calcium ion homeostasis although the specific phosphorylation profiles varied. Figures depict union pathways of proteins phosphorylated in response to EE2 (a) and LNG (b) and their interactions with significantly enriched (p < 0.05) cell processes (gray boxes) as determined by subnetwork enrichment analysis using Pathway Studio 9 (Ariadne Genomics) operating on the ResNet 10.0 mammalian database. Proteins exhibiting increased phosphorylation are colored red, proteins exhibiting decreased phosphorylation are colored green, and phosphoproteins that were not identified in a specific treatment are colored gray. Red linkages indicate up-regulation, green linkages indicate down-regulation, and gray linkages indicate unknown regulation.