Human estrogen receptor alpha / ESR1

evidence_span

{"source_cache": "artifacts/dim-research/37834026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443", "start_char": 0, "end_char": 1593, "text_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443"}

experimental_model

ChIP sequencing and transcriptomics

exposure

DIM, estradiol, TCDD and resveratrol comparisons

limitations

Genome-wide cell-model binding and transcription; no patient efficacy or universal receptor hierarchy established.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human MCF-7 cells

plain_language

Two receptors can cooperate on a response instead of acting as isolated switches.

primary_references

[dim-p37834026] Resveratrol and 3,3'-Diindolylmethane Differentially Regulate Aryl Hydrocarbon Receptor and Estrogen Receptor Alpha Activity through Multiple Transcriptomic Targets in MCF-7 Human Breast Cancer Cells. (2023). https://pubmed.ncbi.nlm.nih.gov/37834026/ DOI: 10.3390/ijms241914578

tissue_or_cell_type

AhR-ERalpha co-regulation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 649–660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ChIP sequencing and transcriptomics · source_derived_draft · unverified_draft

### dim-ahr-er-crosstalk DIM produced overlapping AHR- and ERalpha-associated regulatory patterns, with preferential AHR recruitment to ERalpha targets when both receptors were activated. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two receptors can cooperate on a response instead of acting as isolated switches. organism: Human MCF-7 cells tissue_or_cell_type: AhR-ERalpha co-regulation experimental_model: ChIP sequencing and transcriptomics limitations: Genome-wide cell-model binding and transcription; no patient efficacy or universal receptor hierarchy established. exposure: DIM, estradiol, TCDD and resveratrol comparisons evidence_span: {"source_cache": "artifacts/dim-research/37834026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443", "start_char": 0, "end_char": 1593, "text_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443"} [dim-p37834026] Resveratrol and 3,3'-Diindolylmethane Differentially Regulate Aryl Hydrocarbon Receptor and Estrogen Receptor Alpha Activity through Multiple Transcriptomic Targets in MCF-7 Human Breast Cancer Cells. (2023). https://pubmed.ncbi.nlm.nih.gov/37834026/ DOI: 10.3390/ijms241914578

evidence_span

{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}

experimental_model

Gene expression, chromatin, inhibitors and growth assays

exposure

DIM 10 versus 50 micromolar; estradiol absent

limitations

The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human MCF-7 and T47D cells

plain_language

DIM cannot be described as a universal estrogen blocker.

primary_references

[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

tissue_or_cell_type

ERalpha and proliferation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 597–608

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft

### dim-eralpha-activation DIM at 10 micromolar activated ERalpha-regulated transcription in the absence of estradiol. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: DIM cannot be described as a universal estrogen blocker. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

evidence_span

{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}

experimental_model

Gene expression, chromatin, inhibitors and growth assays

exposure

DIM 10 versus 50 micromolar; estradiol absent

limitations

The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human MCF-7 and T47D cells

plain_language

A kinase pathway connected exposure to receptor signaling.

primary_references

[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

tissue_or_cell_type

ERalpha and proliferation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 623–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft

### dim-pka-eralpha The PKA signaling pathway participated in DIM-mediated ERalpha activation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase pathway connected exposure to receptor signaling. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

evidence_access

Primary abstract

experimental_model

Receptor binding and CHO-K1 reporter experiments.

limitations

No demonstrated hormone normalization in humans.

nutrient_topic

Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol

plain_language

It can interact with hormone receptors, but weak affinity matters.

primary_references

Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 398–404

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Receptor binding and CHO-K1 reporter experiments. · source_derived_draft · unverified_draft

## resveratrol-er-binding It can interact with hormone receptors, but weak affinity matters. Resveratrol bound ERalpha and ERbeta with comparable affinity, approximately 7,000-fold weaker than estradiol in the reported assays. Model: Receptor binding and CHO-K1 reporter experiments. Limitations: No demonstrated hormone normalization in humans. Evidence access: Primary abstract Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721

evidence_span

{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}

experimental_model

Gene expression, chromatin, inhibitors and growth assays

exposure

DIM 10 versus 50 micromolar; estradiol absent

limitations

The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human MCF-7 and T47D cells

plain_language

A growth-promoting response appeared under one defined hormonal condition.

primary_references

[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

tissue_or_cell_type

ERalpha and proliferation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 610–621

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft

### dim-eralpha-proliferation DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A growth-promoting response appeared under one defined hormonal condition. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524

evidence_span

{"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"}

experimental_model

Ligand binding, nuclear complex, transcription and growth assays

exposure

DIM 10-50 micromolar in cells; rodent dosing separately

limitations

Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human MCF-7 cells and rat mammary-tumor model

plain_language

Its effect depended on the hormonal conditions being tested.

primary_references

[dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631

tissue_or_cell_type

AhR and estrogen-responsive signaling

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 311–322

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, nuclear complex, transcription and growth assays · source_derived_draft · unverified_draft

### dim-estrogen-growth-inhibition DIM inhibited estradiol-induced MCF-7 proliferation in the tested estrogen-stimulated system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Its effect depended on the hormonal conditions being tested. organism: Human MCF-7 cells and rat mammary-tumor model tissue_or_cell_type: AhR and estrogen-responsive signaling experimental_model: Ligand binding, nuclear complex, transcription and growth assays limitations: Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established. exposure: DIM 10-50 micromolar in cells; rodent dosing separately evidence_span: {"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"} [dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"}

experimental_model

Transcript-specific expression, haplotype and chromatin-binding analyses

exposure

Estrogen stimulation across PEMT haplotypes

limitations

Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.

nutrient_topic

Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline

organism

Human

plain_language

The hormone signal could not engage this regulatory site normally.

primary_references

[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922

tissue_or_cell_type

Primary hepatocytes and PEMT regulatory locus

trigger_kind

machinery_impairment Imported condition classification; unverified.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 854–865

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transcript-specific expression, haplotype and chromatin-binding analyses · source_derived_draft · unverified_draft

### choline-pemt-esr-binding The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone signal could not engage this regulatory site normally. organism: Human tissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus experimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses limitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response. exposure: Estrogen stimulation across PEMT haplotypes evidence_span: {"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"} [choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922

evidence_access

Primary abstract

experimental_model

Transfected CHO-K1 reporter cells.

limitations

Normal experimental context dependence, not an unresolved contradiction.

nutrient_topic

Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol

plain_language

Direction depends on receptor and gene-control sequence.

primary_references

Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 406–412

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transfected CHO-K1 reporter cells. · source_derived_draft · unverified_draft

## resveratrol-er-sequence Direction depends on receptor and gene-control sequence. Resveratrol acted as an estrogen agonist in ERalpha/ERbeta reporter systems; selected ERE sequences also showed estradiol antagonism with ERalpha but not ERbeta. Model: Transfected CHO-K1 reporter cells. Limitations: Normal experimental context dependence, not an unresolved contradiction. Evidence access: Primary abstract Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11014220/ · DOI 10.1210/endo.141.10.7721

dose

Tartrazine concentration response; reported EC50 160 nM

duration

Reporter exposure interval not specified in accessed abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Human ESR1-positive MCF-7 breast cancer cells

limitations

Reporter activation is not direct receptor-binding proof or demonstrated estrogenic disease in humans; the proposed link to primary biliary disease remains a hypothesis.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Human ESR1-positive MCF-7 breast cancer cells

plain_language

Tartrazine activated the human ER-alpha reporter in MCF-7 cells, with a reported EC50 of 160 nM.

primary_references

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity. (2012). https://pubmed.ncbi.nlm.nih.gov/22562034/ DOI: 10.1016/j.tox.2012.04.014

route

In vitro cell exposure

tissue

Estrogen-response-element reporter

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 270–279

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human ESR1-positive MCF-7 breast cancer cells · source_derived_draft · unverified_draft

## tartrazine-estrogen-reporter Tartrazine activated the human ER-alpha reporter in MCF-7 cells, with a reported EC50 of 160 nM. Model/species: Human ESR1-positive MCF-7 breast cancer cells Tissue: Estrogen-response-element reporter Exposure: Tartrazine concentration response; reported EC50 160 nM Route: In vitro cell exposure Duration: Reporter exposure interval not specified in accessed abstract Limits: Reporter activation is not direct receptor-binding proof or demonstrated estrogenic disease in humans; the proposed link to primary biliary disease remains a hypothesis. Primary reference: Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity. (2012). https://pubmed.ncbi.nlm.nih.gov/22562034/ DOI: 10.1016/j.tox.2012.04.014 Access: Primary PubMed abstract; unrecovered method details explicitly retained.