{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T15:14:02Z","timestamp":1768835642904,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["29139857"],"award-info":[{"award-number":["29139857"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>An inappropriate response to progestogens in the human endometrium can result in fertility issues and jeopardize progestin-based treatments against pathologies such as endometriosis. PGRMC1 can mediate progesterone response in the breast and ovaries but its endometrial functions remain unknown. AG-205 is an alleged PGRMC1 inhibitor but its specificity was recently questioned. We added AG-205 in the cultures of two endometrial cell lines and performed a transcriptomic comparison. AG-205 significantly increased expression of genes coding enzymes of the cholesterol biosynthetic pathway or of steroidogenesis. However, these observations were not reproduced with cells transfected with siRNA against PGRMC1 or its related proteins (MAPRs). Furthermore, AG-205 retained its ability to increase expression of selected target genes even when expression of PGRMC1 or all MAPRs was concomitantly downregulated, indicating that neither PGRMC1 nor any MAPR is required to mediate AG-205 effect. In conclusion, although AG-205 has attractive effects encouraging its use to develop therapeutic strategies, for instance against breast cancer, our study delivers two important warning messages. First, AG-205 is not specific for PGRMC1 or other MAPRs and its mechanisms of action remain unclear. Second, due to its effects on genes involved in steroidogenesis, its use may increase the risk for endometrial pathologies resulting from imbalanced hormones concentrations.<\/jats:p>","DOI":"10.3390\/biom11101472","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T10:36:57Z","timestamp":1633516617000},"page":"1472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["AG-205 Upregulates Enzymes Involved in Cholesterol Biosynthesis and Steroidogenesis in Human Endometrial Cells Independently of PGRMC1 and Related MAPR Proteins"],"prefix":"10.3390","volume":"11","author":[{"given":"Charlotte","family":"Thieffry","sequence":"first","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Van Wynendaele","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asena","family":"Aynaci","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-1852","authenticated-orcid":false,"given":"Mauriane","family":"Maja","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Dupuis","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axelle","family":"Loriot","sequence":"additional","affiliation":[{"name":"GEPI Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne","family":"Marbaix","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"},{"name":"Pathology Department, Cliniques Universitaires Saint-Luc, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Henriet","sequence":"additional","affiliation":[{"name":"CELL Unit, de Duve Institute and Universit\u00e9 Catholique de Louvain, B-1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2174\/138920312804142110","article-title":"Functions of MAPR (membrane-associated progesterone receptor) family members as heme\/steroid-binding proteins","volume":"13","author":"Kimura","year":"2012","journal-title":"Curr. 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Available online: https:\/\/figshare.com\/s\/256ad96e895af6eaab9c.","DOI":"10.3390\/biom11101472"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/10\/1472\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:09:49Z","timestamp":1760166589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/10\/1472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["biom11101472"],"URL":"https:\/\/doi.org\/10.3390\/biom11101472","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]}}}