Estrogen receptor reduces CYP1A1 induction in cultured human endometrial cells

M. Ricci, M S Ricci, D G Toscano, Diane G. Toscano, Carolyn Mattingly, C J Mattingly, W A Toscano, William A. Toscano
Journal of Biological Chemistry · 1999 · vol. 274(6) , pp. 3430–3438 · doi:10.1074/jbc.274.6.3430 · PMID:9920887 · W2156479349
Lab / animal OA: hybrid CC0 ⤵ 5 in-corpus citations
🔓 Open OA copy View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-09 ⓘ

17β-estradiol significantly reduced TCDD-induced CYP1A1 activity and mRNA levels in cultured human endometrial cells by inhibiting transcription.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exerts its toxic action via the aryl hydrocarbon (Ah) receptor, which induces a battery of xenobiotic-metabolizing enzymes, including the cytochrome P450 isozyme, CYP1A1. TCDD-induced 7-ethoxycoumarin-O-deethylase activity was reduced 75% in cultured human endometrial ECC-1 cells exposed to various concentrations of 17beta-estradiol for up to 72 h, with a half-maximal effective concentration (EC50) of 0.9 nM. Reduced enzyme activity was correlated with decreased CYP1A1 mRNA levels, and transcription. Exposure to TCDD plus 17beta-estradiol also reduced CYP1A1 activity in MCF-7 breast cancer cells but not in Hep-3B human liver cells or HuE primary human keratinocytes, suggesting that the effect was specific to estrogen-regulated cells. Estrogen receptor antagonists 4-hydroxytamoxifen and 7alpha-[9-(4,4, 5,5,5-pentafluoro-pentylsulfinyl)nonyl]estra-1,3,5(10)-tr iene3, 17beta-diol restored TCDD-induced CYP1A1 transcription, steady-state mRNA levels, and enzymatic activity in ECC-1 cells. Gel mobility shift assay showed that 17beta-estradiol had little effect on Ah receptor binding to its DNA-responsive element. 17beta-Estradiol did not alter the induction of another Ah receptor-regulated gene, CYP1B1, suggesting that altered Ah receptor binding to DNA does not mediate reduced CYP1A1 transcription. Transfecting ECC-1 cells with a general transcription factor involved in CYP1A1 induction, nuclear factor-1, reversed 17beta-estradiol antagonism of dioxin induced-CYP1A1. The data suggest that 17beta-estradiol reduced CYP1A1 expression at the transcriptional level by squelching available nuclear factor-1, a transcription factor that interacts with both Ah and estrogen receptors.

My notes (saved in your browser only)

MeSH descriptors

Cytochrome P-450 CYP1A1 Endometrium Receptors, Estrogen Cell Line Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A1 Endometrium Endometrium Endometrium Enzyme Induction Estradiol Estradiol Female Humans Polychlorinated Dibenzodioxins Polychlorinated Dibenzodioxins Receptors, Estrogen RNA, Messenger RNA, Messenger Transcription, Genetic

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (78)

Cited by (5)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T22:00:54.229014+00:00
License: CC0 · commercial use OK