Elizabeth Ann L. Enninga, BS, Shernan G. Holtan, MD, Douglas J

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Immunomodulatory Effects of Sex Hormones: Requirements for Pregnancy and Relevance in Melanoma Elizabeth Ann L. Enninga, BS, Shernan G. Holtan, MD, Douglas J. Creedon, MD, PhD, Roxana S. Dronca, MD, Wendy K. Nevala, MS, Simona Ognjanovic, PhD, Svetomir N. Markovic, MD, PhD Mayo Clinic Proceedings Volume 89, Issue 4, Pages 520-535 (April 2014) DOI: 10.1016/j.mayocp.2014.01.006 Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Hormonal changes (in weeks) important for the regulation of gestation in healthy pregnant women. CRH = corticotropin-releasing hormone; hCG = human chorionic gonadotropin. Mayo Clinic Proceedings 2014 89, 520-535DOI: (10.1016/j.mayocp.2014.01.006) Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Effects of sex hormones during early pregnancy to promote implantation and fetal tolerance and the proposed role in initiation of cancer. CRH = corticotropin-releasing hormone; E2 = estradiol; hCG = human chorionic gonadotropin; IFN-γ = interferon gamma; Treg = regulatory T; uNK = uterine natural killer; VEGFR = vascular endothelial growth factor receptor. Mayo Clinic Proceedings 2014 89, 520-535DOI: (10.1016/j.mayocp.2014.01.006) Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Maintenance and regulation of tolerance by sex hormones during midpregnancy and the proposed role of hormones in progression/metastasis of cancer. CRH = corticotropin-releasing hormone; C3 = complement component 3; ER = estrogen receptor; E2 = estradiol; E3 = estrone; hCG = human chorionic gonadotropin; IFN-γ = interferon gamma; PlBF = placental binding factor; TNF-α = tumor necrosis factor alpha; VEGF = vascular endothelial growth factor. Mayo Clinic Proceedings 2014 89, 520-535DOI: (10.1016/j.mayocp.2014.01.006) Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Role of sex hormones in the promotion of inflammation and labor as a natural method for provoking regression of tumor in patients with cancer. bFGF = basic fibroblast growth factor; CRH = corticotropin-releasing hormone; CRHBP = corticotropin-releasing hormone binding protein; E2 = estradiol; hCG = human chorionic gonadotropin; hPRL = human prolactin; IFN-γ = interferon gamma; PR = progesterone receptor; TNF-α = tumor necrosis factor alpha; VEGF = vascular endothelial growth factor. Mayo Clinic Proceedings 2014 89, 520-535DOI: (10.1016/j.mayocp.2014.01.006) Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions