{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:35:49Z","timestamp":1791070549566,"version":"4.1.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p>The breast cancer resistance protein (BCRP) is abundant in the placenta and protects the fetus by limiting placental drug penetration. We hypothesize that pregnancy-specific hormones regulate BCRP expression. Hence, we examined the effects of progesterone (P<jats:sub>4<\/jats:sub>) and 17\u03b2-estradiol (E<jats:sub>2<\/jats:sub>) on BCRP expression in the human placental BeWo cells. P<jats:sub>4<\/jats:sub>and E<jats:sub>2<\/jats:sub>significantly increased and decreased BCRP protein and mRNA, respectively. Likewise, treatment with P<jats:sub>4<\/jats:sub>and E<jats:sub>2<\/jats:sub>increased and decreased, respectively, fumitremorgin C-inhibitable mitoxantrone efflux activity of BeWo cells. Reduction in BCRP expression by E<jats:sub>2<\/jats:sub>was abrogated by the estrogen receptor (ER) antagonist ICI-182,780. However, the progesterone receptor (PR) antagonist RU-486 had no effect on P<jats:sub>4<\/jats:sub>-mediated induction of BCRP. P<jats:sub>4<\/jats:sub>together with E<jats:sub>2<\/jats:sub>further increased BCRP protein and mRNA compared with P<jats:sub>4<\/jats:sub>treatment alone. This combined effect on BCRP expression was abolished by RU-486, ICI-182,780, or both. Further analysis revealed that E<jats:sub>2<\/jats:sub>significantly decreased ER\u03b2 mRNA and strongly induced PR<jats:sub>B<\/jats:sub>mRNA in a dose-dependent manner but had no effect on PR<jats:sub>A<\/jats:sub>and ER\u03b1. P<jats:sub>4<\/jats:sub>alone had no significant effect on mRNA of ER\u03b1, ER\u03b2, PR<jats:sub>A<\/jats:sub>, and PR<jats:sub>B<\/jats:sub>. E<jats:sub>2<\/jats:sub>in combination with P<jats:sub>4<\/jats:sub>increased PR<jats:sub>B<\/jats:sub>mRNA, but the level of induction was significantly reduced compared with E<jats:sub>2<\/jats:sub>treatment alone. Taken together, these results indicate that E<jats:sub>2<\/jats:sub>by itself likely downregulates BCRP expression through an ER, possibly ER\u03b2. P<jats:sub>4<\/jats:sub>alone upregulates BCRP expression via a mechanism other than PR. P<jats:sub>4<\/jats:sub>in combination with E<jats:sub>2<\/jats:sub>further increases BCRP expression, presumably via a nonclassical PR- and\/or E<jats:sub>2<\/jats:sub>-mediated synthesis of PR<jats:sub>B<\/jats:sub>.<\/jats:p>","DOI":"10.1152\/ajpendo.00397.2005","type":"journal-article","created":{"date-parts":[[2005,12,14]],"date-time":"2005-12-14T02:29:17Z","timestamp":1134527357000},"page":"E798-E807","source":"Crossref","is-referenced-by-count":135,"title":["Regulation of BCRP\/ABCG2 expression by progesterone and 17\u03b2-estradiol in human placental BeWo cells"],"prefix":"10.1152","volume":"290","author":[{"given":"Honggang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshul","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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