{"id":4521,"date":"2026-08-21T18:20:49","date_gmt":"2026-08-21T18:20:49","guid":{"rendered":"https:\/\/pge2-hypothesis.com\/?page_id=4521"},"modified":"2026-08-22T19:33:58","modified_gmt":"2026-08-22T19:33:58","slug":"%e2%86%92the-proposed-mechanism","status":"publish","type":"page","link":"https:\/\/pge2-hypothesis.com\/?page_id=4521","title":{"rendered":"\u2192The proposed mechanism"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"4521\" class=\"elementor elementor-4521\">\n\t\t\t\t<div class=\"elementor-element elementor-element-fa10e87 e-flex e-con-boxed e-con e-parent\" data-id=\"fa10e87\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-14c45b9 elementor-widget elementor-widget-heading\" data-id=\"14c45b9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">The proposed mechanism\n\n<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-7734f92 elementor-widget elementor-widget-text-editor\" data-id=\"7734f92\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t<h4><br \/>The proposed mechanism of persisting PGE2 upregulation<\/h4><p>Prostaglandin E2 (PGE2) is a major lipid mediator of inflammation and plays important roles in both acute and chronic immune responses. It acts through four EP receptors\u2014EP1, EP2, EP3 and EP4\u2014which have distinct and sometimes opposing effects on immune and physiological functions.<br \/>During acute inflammation, PGE2 contributes to protective responses that help the body respond to infection or tissue injury. We propose that when PGE2 upregulation persists, however, prolonged PGE2 signaling may progressively alter EP-receptor expression and other signaling networks, disrupting the feedback mechanisms that normally restore homeostasis. <br \/>This could potentially turn a normally transient inflammatory response into a self-sustaining state of PGE2-driven dysregulation.<\/p><p>Acute trigger<br \/>\u2193<br \/>PGE2 upregulation<br \/>\u2193<br \/>Adaptation of the four EP-receptors\u00a0<br \/>\u2193<br \/>Persistent PGE2 upregulation\/activity<br \/>\u2193<br \/>PGE2 <a href=\"https:\/\/pge2-hypothesis.com\/?page_id=4711&amp;preview_id=4711&amp;preview_nonce=ea43e568e8&amp;preview=true\">antagonizes<\/a> other hormones and agents that stimulate PGE2 production<br \/>\u2193<br \/>&#8220;Hormonal Multi-Resistance&#8221;<br \/>\u2193<br \/>Chronic immune and physiological dysregulation leading to 200+ symptoms across different subphenotypes<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-cc7a73b e-flex e-con-boxed e-con e-parent\" data-id=\"cc7a73b\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>The proposed mechanism The proposed mechanism of persisting PGE2 upregulation Prostaglandin E2 (PGE2) is a major lipid mediator of inflammation [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"","ast-site-content-layout":"full-width-container","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"disabled","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center 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