{"id":3064,"date":"2026-04-20T13:25:41","date_gmt":"2026-04-20T13:25:41","guid":{"rendered":"https:\/\/pge2-hypothesis.com\/?page_id=3064"},"modified":"2026-08-15T13:39:23","modified_gmt":"2026-08-15T13:39:23","slug":"elementor-3064","status":"publish","type":"page","link":"https:\/\/pge2-hypothesis.com\/?page_id=3064","title":{"rendered":"Gender, steroids and EP3-capacity"},"content":{"rendered":"\t\t
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Could gender and sex steroids contribute to differing EP3 capacity?<\/h2>\t\t\t\t<\/div>\n\t\t\t\t
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Male and female sexes appear to be overrepresented in the \u201cEP3 up\u201d and \u201cEP3 down\u201d categories, respectively. Greater EP3 expression in males and reduced EP3 expression in females may provide a mechanistic explanation for the following findings:
Male patients are, on average, more vulnerable to severe COVID-19 than female patients1<\/sup> and among male infants, the mortality rate following infections is higher than among female infants2<\/sup>.<\/p>\n

The general symptoms of viral infection are stimulated through EP33<\/sup>. Among female LC patients and among female infants, the prevalence of autoimmune conditions is higher2<\/sup>. Autoimmune responses are primarily stimulated through EP4 and EP2 4,5<\/sup> (see section 5.1.1).<\/p>\n

Estrogen alone or in combination with progesterone has been reported to modulate EP receptor expression and mRNA levels in bovine tissues6<\/sup>. These findings raise the possibility that developmental or hormonal changes in sex steroid levels may also influence EP receptor balance in humans particularly during puberty. Within the framework of the PGE2 hypothesis, such sex-hormone-dependent modulation could contribute to sex-related differences in clinical presentation and may also be relevant to age-specific patterns observed between younger children (6 – <\/strong>11 years) and peri-pubertal adolescents (12 – <\/strong>17 years) with Long COVID7,8<\/sup>.<\/p>\n\n

If women are indeed found to have, on average, significantly lower EP3 capacity compared to men, leading to proportionally greater capacity through EP2 and EP4, this could help explain sex-based medical differences observed in LC and its comorbidities. For more detailed information on hypothetical EP receptor expression clusters and supporting references, see Hypothetical biomarkers.<\/p>\n\n

1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Ricke-Hoch, M. et al.<\/em> Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease. PLOS ONE<\/em> 16<\/strong>, e0255335 (2021). https:\/\/doi.org\/10.1371\/journal.pone.0255335<\/a><\/p>\n\n

2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Muenchhoff, M. & Goulder, P. J. Sex differences in pediatric infectious diseases. J Infect Dis<\/em> 209 Suppl 3<\/strong>, S120-126 (2014). https:\/\/doi.org\/10.1093\/infdis\/jiu232<\/a><\/p>\n\n

3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Bin, N. R. et al.<\/em> An airway-to-brain sensory pathway mediates influenza-induced sickness. Nature<\/em> 615<\/strong>, 660-667 (2023). https:\/\/doi.org\/10.1038\/s41586-023-05796-0<\/a><\/p>\n\n

4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Tsuge, K., Inazumi, T., Shimamoto, A. & Sugimoto, Y. Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases. Int Immunol<\/em> 31<\/strong>, 597-606 (2019). https:\/\/doi.org\/10.1093\/intimm\/dxz021<\/a><\/p>\n\n

5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Fedyk, E. R. & Phipps, R. P. Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Proc Natl Acad Sci U S A<\/em> 93<\/strong>, 10978-10983 (1996). https:\/\/doi.org\/10.1073\/pnas.93.20.10978<\/a><\/p>\n\n

6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Blesson, C. S., B\u00fcttner, E., Masironi, B. & Sahlin, L. Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats. Reproductive Biology and Endocrinology<\/em> 10<\/strong>, 3 (2012). https:\/\/doi.org\/10.1186\/1477-7827-10-3<\/a><\/p>\n\n

7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Gross, R. S. et al.<\/em> Characterizing Long COVID in Children and Adolescents. Jama<\/em> 332<\/strong>, 1174-1188 (2024). https:\/\/doi.org\/10.1001\/jama.2024.12747<\/a><\/p>\n\n

8\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kikkenborg Berg, S. et al.<\/em> Long COVID symptoms in SARS-CoV-2-positive children aged 0-14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc Health<\/em> 6<\/strong>, 614-623 (2022). https:\/\/doi.org\/10.1016\/s2352-4642(22)00154-7<\/a><\/p>\n\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\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Could gender and sex steroids contribute to differing EP3 capacity? Male and female sexes appear to be overrepresented in the […]<\/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":"default","site-content-layout":"","ast-site-content-layout":"default","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":"","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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"class_list":["post-3064","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/3064","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3064"}],"version-history":[{"count":11,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/3064\/revisions"}],"predecessor-version":[{"id":4391,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/3064\/revisions\/4391"}],"wp:attachment":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3064"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}