Affinage

CYP19A1

Aromatase · UniProt P11511

Length
503 aa
Mass
57.9 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP19A1 encodes aromatase, a microsomal cytochrome P450 that is the single enzyme catalyzing the three successive oxidations converting androgens to estrogens, the committed step of estrogen biosynthesis (PMID:4083898, PMID:3182796). Purified placental aromatase reconstituted with NADPH-cytochrome P450 reductase and phospholipid is catalytically active and immunologically distinct from other steroid hydroxylases (PMID:4083898), and heterologous expression of a single cDNA confers full androstenedione-to-estrogen conversion with correct microsomal targeting (PMID:3182796). Catalysis proceeds through an unusual iron peroxy-anion intermediate that is trapped by the substrate C19 aldehyde to cleave the acyl-carbon bond and aromatize the steroid A-ring, distinguishing it from canonical Compound I P450 chemistry (PMID:26002733). Enzyme activity depends on productive electron transfer from POR, as POR FMN-domain and hinge mutations abolish or enhance aromatase activity in reconstituted systems (PMID:28970799), and is further tuned post-translationally by phosphorylation, including activating phosphorylation of Y361 at the reductase-coupling interface (PMID:31652308). Transcription is governed by a network of tissue-specific promoters (PMID:2040633) integrating nuclear-receptor activators (SF-1/NR5A1, LRH-1/NR5A2, ESR1/ESR2, RORα) and repressors (NR1D1, CEBPB, CTBP1/EP300), along with epigenetic and signaling inputs such as SIRT1, CRTC2/calcineurin, HDAC-dependent H3K9 acetylation, and DVL proteins (PMID:23340254, PMID:28347743, PMID:25057110, PMID:34933195, PMID:30152543, PMID:27925372, PMID:34710471, PMID:26213324, PMID:30479694); at the post-transcriptional level CELF1 represses Cyp19a1 mRNA translation while METTL3/eIF4E promotes it via m6A (PMID:26169831, PMID:38238831). Functionally, aromatase-derived estrogen drives gonadal sex differentiation, being necessary and sufficient for female development in the avian gonad (PMID:32990306), controls intratesticular testosterone required for spermiogenesis (PMID:26169831), and contributes to pathological estrogen production in cancers and to sex-biased COVID-19 lung pathology (PMID:30152543, PMID:37572667). Loss-of-function splicing mutations that cripple aromatase activity underlie human aromatase deficiency (PMID:1371509).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1985 High

    Established that aromatase is a discrete P450 protein and the catalytically active subunit, answering whether estrogen synthesis required a dedicated enzyme.

    Evidence Immunoaffinity purification of 55-kDa placental protein, reconstitution with NADPH-P450 reductase and phospholipid, antibody inhibition with specificity controls

    PMID:4083898

    Open questions at the time
    • Did not resolve whether one protein performs all three oxidations
    • No structural or mechanistic detail of catalysis
  2. 1988 High

    Demonstrated that a single CYP19A1 gene product catalyzes all three oxidation steps from androgen to estrogen, settling the one-enzyme question.

    Evidence Heterologous expression of chicken CYP19A1 cDNA in COS-1 cells with microsomal activity assay and subcellular fractionation

    PMID:3182796

    Open questions at the time
    • Chemical mechanism of acyl-carbon cleavage not defined
    • Regulation in vivo not addressed
  3. 1991 High

    Revealed that tissue-specific aromatase expression is driven by alternative promoters, explaining how the same enzyme is differentially produced across tissues.

    Evidence RT-PCR, primer extension, S1 nuclease protection and Northern blot of placental vs adipose transcripts

    PMID:2040633

    Open questions at the time
    • Trans-acting factors driving each promoter not identified here
    • Did not address regulation in disease
  4. 1992 High

    Linked a CYP19A1 splice mutation directly to human aromatase deficiency, establishing the gene as the disease locus.

    Evidence Patient cDNA sequencing, Northern/Western blot, expression of mutant cDNA in COS-7 with activity assay

    PMID:1371509

    Open questions at the time
    • Single patient mutation
    • Genotype-phenotype spectrum not defined
  5. 2015 Medium

    Defined the unusual acyl-carbon cleavage chemistry of aromatization, distinguishing CYP19A1 from canonical monooxygenase P450s.

    Evidence Mechanistic biochemistry review synthesizing isotopic, substrate-analog and structural studies

    PMID:26002733

    Open questions at the time
    • Review rather than new primary experiment
    • Intermediate species not directly observed in this work
  6. 2015 High

    Identified CELF1-mediated translational repression of Cyp19a1 as a post-transcriptional control point governing intratesticular testosterone and spermiogenesis.

    Evidence RNA-binding and reporter assays, Celf1 knockout mice, hormone measurement, testosterone/letrozole rescue

    PMID:26169831

    Open questions at the time
    • CELF1 binding element on Cyp19a1 mRNA not mapped
    • Translational machinery involved not detailed
  7. 2017 High

    Showed POR electron-transfer function controls aromatase output, with FMN-domain and hinge mutations bidirectionally modulating activity.

    Evidence Bacterial expression, liposome reconstitution of WT/mutant POR with CYP19A1, kinetics, cytochrome c reduction, flavin content

    PMID:28970799

    Open questions at the time
    • Structural basis of altered POR-CYP19A1 interaction not solved
    • Tissue-level consequences not tested
  8. 2017 Medium

    Mapped multiple nuclear-receptor and signaling regulators (SF-1, RORα, LRH-1, LPS/CEBPB) to specific CYP19A1 promoter elements, building the transcriptional network.

    Evidence ChIP, luciferase reporters, overexpression/knockdown and ligand/pathway-inhibitor experiments in granulosa, theca, monocyte and endothelial systems

    PMID:27925372 PMID:28347743 PMID:28412504 PMID:29378329

    Open questions at the time
    • Largely single-lab, non-human cell systems
    • Combinatorial promoter logic across factors not integrated
  9. 2019 High

    Established phosphorylation, including activating Y361 at the reductase interface, as a post-translational regulator of aromatase activity.

    Evidence Phosphoproteomic mass spectrometry of placental aromatase with biochemical activity assay and structural analysis

    PMID:31652308

    Open questions at the time
    • Kinases responsible not identified
    • Physiological stimuli driving phosphorylation unknown
  10. 2019 Low

    Reported plasma-membrane localization of CYP19A1 in addition to the ER, raising the possibility of non-canonical surface display.

    Evidence Flow cytometry/immunological detection on MCF-7 and MCF-10A cells, autoantibody ELISA

    PMID:31082724

    Open questions at the time
    • Single immunological method without orthogonal confirmation
    • No functional consequence assigned to surface localization
  11. 2020 High

    Demonstrated that CYP19A1 is necessary and sufficient to initiate female gonadal sex differentiation in vivo.

    Evidence Lentiviral knockdown and overexpression in chicken embryos, aromatase inhibitor, immunohistochemistry, gonadal phenotyping

    PMID:32990306

    Open questions at the time
    • Mammalian relevance not addressed
    • Upstream initiating cue for dimorphic expression unresolved
  12. 2023 Medium

    Expanded CYP19A1's pathophysiology beyond reproduction, linking elevated pulmonary aromatase to sex-biased COVID-19 severity.

    Evidence Hamster infection model with letrozole treatment, human autopsy IHC, exome sequencing with machine learning, hormone and lung-function assays

    PMID:37572667

    Open questions at the time
    • Mechanism of pulmonary CYP19A1 induction unclear
    • Causality of the activating mutation not functionally proven

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse transcriptional, translational (m6A), and post-translational inputs are integrated into a coherent, tissue- and context-specific control of aromatase output remains unresolved.
  • No unified model linking promoter choice, phosphorylation, and POR coupling
  • Human structural mechanism of acyl-carbon cleavage not directly visualized in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0016740 transferase activity 3
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1430728 Metabolism 3 R-HSA-1266738 Developmental Biology 2
Partners
CELF1ESR1ESR2METTL3NR5A1NR5A2PORRORA

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 Human aromatase (CYP19A1/P-450AROM) was identified as a 55-kDa protein in placental microsomes. Purified protein reconstituted with NADPH-cytochrome P450 reductase and phospholipid displayed aromatase catalytic activity, establishing it as the enzymatically active subunit. Polyclonal IgG against the 55-kDa protein inhibited aromatase activity by 80% with no effect on 17α-hydroxylase or 21-hydroxylase, demonstrating enzymatic specificity. Immunoaffinity chromatography, enzyme reconstitution with purified NADPH-cytochrome P450 reductase and phospholipid, immunoblot, antibody inhibition assay Archives of biochemistry and biophysics High 4083898
1988 Expression of a chicken CYP19A1 cDNA in COS-1 cells produced high levels of aromatase activity, demonstrating that the single protein catalyzes all three successive oxidation reactions required to convert androgen (androstenedione) to estrogen. The enzyme was correctly targeted to microsomal fractions in transfected cells, with Km similar to native chicken ovarian enzyme. Heterologous cDNA expression in COS-1 cells, microsomal aromatase activity assay, subcellular fractionation The Journal of biological chemistry High 3182796
1991 The CYP19A1 gene uses tissue-specific promoters: placenta uses upstream untranslated exons I.1 and I.2 with their associated promoters, whereas adipose tissue uses a distinct promoter approximately 110 bp upstream of exon II with a transcription start site 26 bp downstream of a TATAAA element. These alternative promoters drive tissue-specific aromatase expression. RT-PCR, primer extension analysis, S1 nuclease protection assay, Northern blotting The Journal of biological chemistry High 2040633
1992 A point mutation at the splice consensus sequence between exon 6 and intron 6 (GT→GC) caused aberrant splicing, inserting 87 bp of intronic sequence encoding 29 extra amino acids in-frame into aromatase mRNA. The resulting abnormal protein had trace aromatase activity when expressed in COS-7 cells, establishing that this splicing mutation is the molecular basis of aromatase deficiency in this patient. cDNA library sequencing, Northern blot, Western blot, transient expression in COS-7 cells, enzyme activity assay The Journal of biological chemistry High 1371509
2015 The acyl-carbon bond cleavage mechanism of CYP19A1 involves the iron peroxy anion intermediate (FeIII-O-O-) being trapped by the substrate's C19 aldehyde carbonyl to form a tetrahedral intermediate, which then fragments to cleave the acyl-carbon bond and release the aromatized estrogen product. This distinguishes the CYP19A1 mechanism from classical P450 monooxygenation that proceeds via Compound I. Mechanistic biochemistry review synthesizing isotopic labeling, substrate analog, and structural studies (Tier 1 compilation) Advances in experimental medicine and biology Medium 26002733
2013 SIRT1 positively regulates CYP19A1 transcription in breast cancer cells. SIRT1 occupies the CYP19A1 promoter regions PI.3/PII and PI.4. Pharmacologic inhibition of SIRT1 or siRNA knockdown reduced aromatase mRNA and protein. SIRT1 inhibition led to increased acetylation of estrogen-related receptor alpha (ERRα), a transcription factor that activates CYP19A1 transcription in epithelial cells. Chromatin immunoprecipitation (ChIP), siRNA knockdown, small-molecule SIRT1 inhibitors, qRT-PCR, Western blot Molecular endocrinology Medium 23340254
2017 In chicken ovary theca cells, the transcription factor SF-1 (NR5A1) directly activates CYP19A1 transcription by binding to a nuclear receptor half-site (5'-TCAAGGTCA-3') located −280 to −271 bp in the CYP19A1 promoter. Overexpression of SF-1 in DF-1 cells upregulated aromatase expression. In contrast, FOXL2 did not activate the CYP19A1 promoter in either 293T or DF-1 cells. Luciferase reporter assay, overexpression in cell lines, RT-PCR General and comparative endocrinology Medium 28347743
2017 Mutations in the FMN-binding domain of P450 oxidoreductase (POR) at positions A115V and T142A nearly abolished CYP19A1 aromatase activity in a reconstituted in vitro system, and reduced flavin content. POR mutation P284L in the hinge region also severely reduced CYP19A1 activity. Conversely, POR mutation Q153R markedly increased CYP19A1 activity without changing flavin content, suggesting improved POR-CYP19A1 protein-protein interaction. Bacterial expression and purification of recombinant proteins, liposome reconstitution, enzyme kinetic assays, cytochrome c reduction assay, flavin content measurement Frontiers in pharmacology High 28970799
2018 DVL1 and DVL3 (Dishevelled proteins, key Wnt signaling mediators) localize to the nucleus and occupy at least two CYP19A1 promoters (pII and I.4) that drive overexpression in breast tumors, as well as the distal placental promoter I.1. Loss of DVL-1 or DVL-3 function led to differential changes in aromatase transcripts and in estradiol production in breast cancer cell lines. Chromatin immunoprecipitation (ChIP), loss-of-function experiments, qRT-PCR, estradiol measurement Oncotarget Medium 30479694
2019 Human placental aromatase CYP19A1 is phosphorylated at multiple sites. Phosphorylation of Y361 at the reductase-coupling interface significantly elevates aromatase catalytic activity. Additional phosphorylation sites include the active-site residue S478 and several membrane-interface residues. Two histidine residues were also found to be phosphorylated. Oxidation of two proline residues near the active site was detected and may regulate activity. Mass spectrometry (phosphoproteomics), biochemical assay, structural data analysis, cellular experiments The Biochemical journal High 31652308
2019 CYP19A1 protein was detected on the plasma membrane of MCF-7 breast cancer cells and of normal MCF-10A breast cells by immunological methods, indicating plasma membrane localization in addition to its canonical endoplasmic reticulum localization. Anti-CYP19A1 autoantibodies were detectable in both breast cancer patients and controls, with no significant group differences. Flow cytometry / immunological detection of cell-surface CYP19A1, indirect ELISA for autoantibodies International immunopharmacology Low 31082724
2014 FSH and TGFβ1 upregulate Cyp19a1 expression in ovarian granulosa cells via calcineurin-mediated dephosphorylation-activation of CRTC2, which binds to the Cyp19a1 PII promoter. LRH1 (NR5A2) and SF1 (NR5A1) protein levels were increased by FSH+TGFβ1, and their binding to the Cyp19a1 PII promoter was demonstrated. Calcineurin auto-inhibitory peptide abolished FSH+TGFβ1-upregulated (but not FSH-alone) aromatase activity, establishing calcineurin as pathway-specific regulator. Chromatin immunoprecipitation (ChIP), calcineurin inhibitory peptide, Western blot, aromatase activity assay, qRT-PCR Journal of molecular endocrinology Medium 25057110
2021 NR1D1 (REV-ERBα), a circadian clock transcriptional repressor, binds to the RORE element on the CYP19A1 promoter in porcine granulosa cells, thereby inhibiting CYP19A1 transcription and reducing estradiol production. NR1D1 activation enhanced this repression, while NR1D1 knockdown relieved it. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, NR1D1 activation/interference experiments, ELISA for estradiol Theriogenology Medium 34933195
2017 LPS activates TLR4 signaling in buffalo granulosa cells, leading to increased CEBPB expression and nuclear translocation. CEBPB binds to the CYP19A1 proximal promoter (PII) and represses CYP19A1 transcription, resulting in decreased estradiol production. TLR4 inhibitor (OxPAPC) attenuated these effects. Chromatin immunoprecipitation (ChIP), TLR4 inhibitor treatment, Western blot, qRT-PCR, ELISA Toxicology in vitro Medium 28412504
2015 The RNA-binding protein CELF1 directly binds Cyp19a1 mRNA and represses its translation. In Celf1 knockout mice, Cyp19a1 is posttranscriptionally upregulated, leading to excessive aromatase activity, reduced testosterone, and impaired spermiogenesis. Administration of testosterone or the aromatase inhibitor letrozole partially rescued the spermiogenesis defects, placing CELF1-mediated translational repression of CYP19A1 in the pathway controlling intratesticular testosterone levels required for spermiogenesis. In vivo/in vitro RNA binding assay, reporter assay for translational repression, Celf1 knockout mouse model, hormone measurements, rescue experiments with testosterone and letrozole Molecular and cellular biology High 26169831
2018 METTL3, an m6A methyltransferase, enhances CYP19A1 mRNA translation efficiency in an m6A-dependent manner in NSCLC cells. METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, promoting aromatase protein synthesis and estrogen production to drive NSCLC metastasis. Pharmacological inhibition of METTL3 or eIF4E abolished CYP19A1 protein synthesis. Translatomics, m6A-seq, RNA immunoprecipitation, co-immunoprecipitation, Western blot, METTL3 knockdown/knockout, eIF4E inhibitor, in vitro and in vivo invasion assays Cell & bioscience Medium 38238831
2018 CTBP1 and EP300 bind to the CYP19A1 promoter in PCa cells and downregulate CYP19A1 expression. Estradiol, acting through estrogen receptor beta, releases CTBP1 from the CYP19A1 promoter, thereby de-repressing CYP19A1 transcription and increasing estradiol production. In CTBP1-depleted PCa xenografts in NSG mice, CYP19A1 expression and intratumoral estradiol were increased. Chromatin immunoprecipitation (ChIP), CTBP1 depletion, xenograft mouse model, hormone measurement, Western blot International journal of cancer Medium 30152543
2017 RORα directly occupies the promoter of CYP19A1 in THP-1 monocytes and HUVEC cells, as shown by ChIP. Modulating RORα activity with specific ligands (CPG 52608 and SR1001) altered CYP19A1 expression, establishing CYP19A1 as a direct RORα target gene. Simvastatin downregulated CYP19A1 expression, and this was partially prevented by RORα ligands. Chromatin immunoprecipitation (ChIP), RORα ligand treatment, qRT-PCR Cell biology international Medium 27925372
2020 In chicken embryos, lentiviral-mediated knockdown of CYP19A1 caused male sex reversal, while overexpression drove female sex differentiation, establishing CYP19A1 as both necessary and sufficient to initiate female gonadal sex differentiation. CYP19A1 showed sexually dimorphic expression in female gonads from embryonic day 5.5, localized to ovarian medullas. Lentiviral in ovo knockdown and overexpression, aromatase inhibitor treatment, immunohistochemistry, gonadal sex phenotype analysis Bioscience reports High 32990306
2021 Transcription factors ESR1, ESR2, and NR5A2 form a functional regulatory network controlling CYP19A1 expression in chicken theca cells. ESR1 and NR5A2 activated the CYP19A1 promoter in luciferase assays; overexpression of ESR1, ESR2, or NR5A2 upregulated CYP19A1 protein and these factors mutually restricted each other. In contrast, FOXL2 did not regulate CYP19A1 expression at embryonic stages or after sexual maturity in chicken. Luciferase reporter assay, overexpression in DF-1 and theca cells, Western blot, immunofluorescence General and comparative endocrinology Medium 34710471
2023 CYP19A1 expression is increased in the lungs of SARS-CoV-2-infected male golden hamsters and in human autopsy lungs of males. A CYP19A1-activity-increasing mutation was associated with severe COVID-19 in men. Increased pulmonary CYP19A1 was associated with dysregulated plasma sex hormones and impaired long-term lung function specifically in males. Treatment with the CYP19A1 inhibitor letrozole improved lung function and restored sex hormone balance in infected male hamsters. Exome sequencing with machine-learning analysis, human autopsy immunohistochemistry, hamster infection model with letrozole treatment, lung function measurement, hormone assays Cell reports. Medicine Medium 37572667
2020 miR-326 inhibits CYP19A1 transcription in buffalo granulosa cells by upregulating CREB, which activates C/EBP-β; increased C/EBP-β then binds the CYP19A1 PII promoter (shown by ChIP) and reduces RNA polymerase II binding, thereby decreasing CYP19A1 mRNA and estradiol-17β production. miRNA mimic transfection, ChIP for C/EBP-β and RNA Pol II at CYP19A1 PII promoter, qRT-PCR, ELISA The Journal of steroid biochemistry and molecular biology Medium 31996328
2015 LPS-mediated inhibition of CYP19A1 expression and estradiol production in granulosa cells involves HDAC-dependent histone deacetylation at H3K9 of the CYP19A1 PII proximal promoter and NF-κB nuclear translocation. The HDAC inhibitor TSA prevented H3 deacetylation at PII (confirmed by ChIP) and restored CYP19A1 expression and estradiol production, placing HDAC activity as a downstream effector of LPS/NF-κB signaling in CYP19A1 repression. HDAC inhibitor (TSA), ChIP for H3(K9/14) acetylation at CYP19A1 PII, NF-κB nuclear translocation assay, qRT-PCR, ELISA Molecular and cellular endocrinology Medium 26213324
2017 LRH-1 (liver receptor homolog-1) protein directly binds the CYP19A1 promoter and increases its transcriptional activity in porcine granulosa cells (shown by luciferase and ChIP assays). miR-1275 targets the 3'UTR of LRH-1 mRNA (not CYP19A1 directly), suppressing LRH-1 expression and thereby reducing CYP19A1 transcription, estradiol synthesis, and promoting granulosa cell apoptosis. Luciferase reporter assay, ChIP, miRNA overexpression/knockdown, in vitro LRH-1 overexpression/knockdown, flow cytometry Biochimica et biophysica acta. Gene regulatory mechanisms Medium 29378329

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 Preparation and characterization of polyclonal and monoclonal antibodies against human aromatase cytochrome P-450 (P-450AROM), and their use in its purification. Archives of biochemistry and biophysics 166 4083898
1991 Construction of genetically defined double aro mutants of Salmonella typhi. Vaccine 156 1759503
1991 Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. The Journal of biological chemistry 152 2040633
2008 The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior. Journal of bacteriology 143 18978044
2024 Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia: The SHASTA-2 Randomized Clinical Trial. JAMA cardiology 138 38583092
1988 The expression of a functional cDNA encoding the chicken cytochrome P-450arom (aromatase) that catalyzes the formation of estrogen from androgen. The Journal of biological chemistry 131 3182796
2008 Systematic deletion of Salmonella small RNA genes identifies CyaR, a conserved CRP-dependent riboregulator of OmpX synthesis. Molecular microbiology 128 18399940
2008 Down-regulation of outer membrane proteins by noncoding RNAs: unraveling the cAMP-CRP- and sigmaE-dependent CyaR-ompX regulatory case. Journal of molecular biology 96 18619465
2022 A Review on CYP11A1, CYP17A1, and CYP19A1 Polymorphism Studies: Candidate Susceptibility Genes for Polycystic Ovary Syndrome (PCOS) and Infertility. Genes 85 35205347
2004 Growth, virulence, and immunogenicity of Listeria monocytogenes aro mutants. Infection and immunity 77 15385459
1992 Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency. The Journal of biological chemistry 75 1371509
2009 Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. The British journal of dermatology 68 19438456
2022 A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis. Journal of hepatology 67 36513186
2013 SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression. Molecular endocrinology (Baltimore, Md.) 62 23340254
2009 Dimorphic expression of dmrt1 and cyp19a1 (ovarian aromatase) during early gonadal development in pejerrey, Odontesthes bonariensis. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 62 19276634
2015 CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer. Endocrine-related cancer 56 26574572
2018 miR-1275 controls granulosa cell apoptosis and estradiol synthesis by impairing LRH-1/CYP19A1 axis. Biochimica et biophysica acta. Gene regulatory mechanisms 47 29378329
2016 Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis. Journal of assisted reproduction and genetics 46 27167072
2013 Promoter methylation of CYP19A1 gene in Chinese polycystic ovary syndrome patients. Gynecologic and obstetric investigation 45 24157654
2011 Aflatoxin B1--a potential endocrine disruptor--up-regulates CYP19A1 in JEG-3 cells. Toxicology letters 43 21296134
2017 Transcription of CYP19A1 is directly regulated by SF-1 in the theca cells of ovary follicles in chicken. General and comparative endocrinology 42 28347743
2006 Genetic polymorphisms of the CYP19A1 gene and breast cancer survival. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 42 17119036
2018 DVL1 and DVL3 differentially localize to CYP19A1 promoters and regulate aromatase mRNA in breast cancer cells. Oncotarget 41 30479694
2013 Expression and sequence evolution of aromatase cyp19a1 and other sexual development genes in East African cichlid fishes. Molecular biology and evolution 41 23883521
2018 Sex-specific dmrt1 and cyp19a1 methylation and alternative splicing in gonads of the protandrous hermaphrodite barramundi. PloS one 40 30226860
2018 An Engineered Aro1 Protein Degradation Approach for Increased cis,cis-Muconic Acid Biosynthesis in Saccharomyces cerevisiae. Applied and environmental microbiology 37 29934332
2008 aro mutations in Salmonella enterica cause defects in cell wall and outer membrane integrity. Journal of bacteriology 37 18310348
2007 Local expression of CYP19A1 and CYP19A2 in developing and adult killifish (Fundulus heteroclitus). General and comparative endocrinology 35 17582409
2018 Malignant transformation of canine oral papillomavirus (CPV1)-associated papillomas in dogs: An emerging concern? Papillomavirus research (Amsterdam, Netherlands) 33 30414951
2009 DNA methylation is not involved in preovulatory down-regulation of CYP11A1, HSD3B1, and CYP19A1 in bovine follicles but may have a role in permanent silencing of CYP19A1 in large granulosa lutein cells. Biology of reproduction 33 19794152
2007 Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in Chinese women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 32 17507620
1988 The Saccharomyces cerevisiae ARO1 gene. An example of the co-ordinate regulation of five enzymes on a single biosynthetic pathway. FEBS letters 32 2848727
2015 HDAC inhibitor prevents LPS mediated inhibition of CYP19A1 expression and 17β-estradiol production in granulosa cells. Molecular and cellular endocrinology 29 26213324
2021 Effect of quorum-sensing molecule 2-phenylethanol and ARO genes on Saccharomyces cerevisiae biofilm. Applied microbiology and biotechnology 28 33852023
2020 2-Anilinopyrimidine derivatives: Design, synthesis, in vitro anti-proliferative activity, EGFR and ARO inhibitory activity, cell cycle analysis and molecular docking study. Bioorganic chemistry 28 32247112
2020 Upregulation of Cyp19a1 and PPAR-γ in ovarian steroidogenic pathway by Ficus religiosa: A potential cure for polycystic ovary syndrome. Journal of ethnopharmacology 28 33152430
2012 Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy. Endocrine 28 22638611
2009 Alternative 5'-untranslated first exons of the mouse Cyp19A1 (aromatase) gene. The Journal of steroid biochemistry and molecular biology 28 19500729
2007 Sex and body mass index specific regulation of blood pressure by CYP19A1 gene variants. Hypertension (Dallas, Tex. : 1979) 28 17893373
2020 Upregulation of miR-146b promotes porcine ovarian granulosa cell apoptosis by attenuating CYP19A1. Domestic animal endocrinology 27 32653739
2015 CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial. Breast cancer research and treatment 27 25935582
2014 Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. The journal of sexual medicine 27 25124466
2014 Calcineurin and CRTC2 mediate FSH and TGFβ1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cells. Journal of molecular endocrinology 26 25057110
2011 Variation in the CYP19A1 gene and risk of colon and rectal cancer. Cancer causes & control : CCC 26 21479914
2009 Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report. Reproductive biomedicine online 26 19549443
2021 NR1D1 targeting CYP19A1 inhibits estrogen synthesis in ovarian granulosa cells. Theriogenology 24 34933195
2019 Nitrophenols suppress steroidogenesis in prehierarchical chicken ovarian follicles by targeting STAR, HSD3B1, and CYP19A1 and downregulating LH and estrogen receptor expression. Domestic animal endocrinology 24 31514021
2017 Altered CYP19A1 and CYP3A4 Activities Due to Mutations A115V, T142A, Q153R and P284L in the Human P450 Oxidoreductase. Frontiers in pharmacology 24 28970799
2016 Polymorphisms in ABCB1 and CYP19A1 genes affect anastrozole plasma concentrations and clinical outcomes in postmenopausal breast cancer patients. British journal of clinical pharmacology 24 27747906
2014 Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival. International journal of cancer 24 24803183
2021 Copper exposure disrupts ovarian steroidogenesis in human ovarian granulosa cells via the FSHR/CYP19A1 pathway and alters methylation patterns on the SF-1 gene promoter. Toxicology letters 23 34871762
2019 Plasma membrane localization of CYP4Z1 and CYP19A1 and the detection of anti-CYP19A1 autoantibodies in humans. International immunopharmacology 23 31082724
2014 A retrospective investigation on canine papillomavirus 1 (CPV1) in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer. PloS one 23 25401953
1998 Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. Surgery 23 9854590
2015 Down-regulation of the CYP19A1 gene in cumulus cells of infertile women with endometriosis. Reproductive biomedicine online 22 25773531
2015 Sex- and Obesity-specific Association of Aromatase (CYP19A1) Gene Variant with Apolipoprotein B and Hypertension. Archives of medical research 22 26415088
2006 Tissue- and sex-specific regulation of CYP19A1 expression in the Atlantic croaker (Micropogonias undulatus). General and comparative endocrinology 22 16872606
2021 New thieno[3,2-d]pyrimidine-based derivatives: Design, synthesis and biological evaluation as antiproliferative agents, EGFR and ARO inhibitors inducing apoptosis in breast cancer cells. Bioorganic chemistry 21 34365057
2019 Sequence variants in FSHR and CYP19A1 genes and the ovarian response to controlled ovarian stimulation. Fertility and sterility 21 31371045
2019 Phosphorylation of human placental aromatase CYP19A1. The Biochemical journal 21 31652308
2008 Haplotype analyses of CYP19A1 gene variants and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 21 18199708
1983 Isolation of the ARO1 cluster gene of Saccharomyces cerevisiae. Molecular and cellular biology 21 6355828
2022 Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth. Cancer medicine 20 35545835
2019 Placental ESRRG-CYP19A1 Expressions and Circulating 17-Beta Estradiol in IUGR Pregnancies. Frontiers in pediatrics 20 31069202
2018 The Importance of CYP19A1 in Estrogen Receptor-Positive Cholangiocarcinoma. Hormones & cancer 20 30284180
2015 Acyl-Carbon Bond Cleaving Cytochrome P450 Enzymes: CYP17A1, CYP19A1 and CYP51A1. Advances in experimental medicine and biology 20 26002733
2020 CYP19A1 (aromatase) dominates female gonadal differentiation in chicken (Gallus gallus) embryos sexual differentiation. Bioscience reports 19 32990306
2018 CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome. International journal of cancer 19 30152543
2023 CYP19A1 mediates severe SARS-CoV-2 disease outcome in males. Cell reports. Medicine 18 37572667
2022 LINC00094/miR-19a-3p/CYP19A1 axis affects the sensitivity of ER positive breast cancer cells to Letrozole through EMT pathway. Aging 18 35657638
2020 Novel CYP19A1 Mutations Extend the Genotype-Phenotype Correlation and Reveal the Impact on Ovarian Function. Journal of the Endocrine Society 17 32318648
2018 Candida albicans Aro1 affects cell wall integrity, biofilm formation and virulence. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 17 29807722
2017 CYP19A1, MIF and ABCA1 genes are targets of the RORα in monocyte and endothelial cells. Cell biology international 17 27925372
2012 AKT-aro and HER2-aro, models for de novo resistance to aromatase inhibitors; molecular characterization and inhibitor response studies. Breast cancer research and treatment 17 22706627
2019 Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression. Depression and anxiety 16 31730745
2018 Association of CYP19A1 gene polymorphisms with anoestrus in water buffaloes. Reproduction, fertility, and development 16 28814372
2014 Cyp19a1 (aromatase) expression in the Xenopus brain at different developmental stages. Journal of neuroendocrinology 16 24612124
2021 Transcriptional regulation of CYP19A1 expression in chickens: ESR1, ESR2 and NR5A2 form a functional network. General and comparative endocrinology 15 34710471
2017 Endotoxin induced TLR4 signaling downregulates CYP19A1 expression through CEBPB in buffalo granulosa cells. Toxicology in vitro : an international journal published in association with BIBRA 15 28412504
2015 Hypogonadism Associated with Cyp19a1 (Aromatase) Posttranscriptional Upregulation in Celf1 Knockout Mice. Molecular and cellular biology 15 26169831
2012 Association between CYP19A1 genotype and pubertal sagittal jaw growth. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 15 23116507
2022 The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis. Frontiers in physiology 14 35615684
2014 Cell-mass structures expressing the aromatase gene Cyp19a1 lead to ovarian cavities in Xenopus laevis. Endocrinology 14 25051437
1985 Cloning of the ARO cluster gene of Neurospora crassa and its expression in Escherichia coli. Molecular & general genetics : MGG 14 2993794
2019 Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene. Endocrine 13 31325085
2016 Enzymatic and Inhibition Mechanism of Human Aromatase (CYP19A1) Enzyme. A Computational Perspective from QM/MM and Classical Molecular Dynamics Simulations. Mini reviews in medicinal chemistry 13 27337972
2001 3D H(aro)-NOESY-CH3NH and C(aro)-NOESY-CH3NH experiments for double labeled proteins. Journal of biomolecular NMR 13 11370781
2024 METTL3 drives NSCLC metastasis by enhancing CYP19A1 translation and oestrogen synthesis. Cell & bioscience 12 38238831
2018 Aromatase Deficiency due to a Novel Mutation in CYP19A1 Gene. Journal of clinical research in pediatric endocrinology 12 29553041
2022 CYP19A1 May Influence Lambing Traits in Goats by Regulating the Biological Function of Granulosa Cells. Animals : an open access journal from MDPI 11 35953905
2021 Ovarian Toxicity Induced by Aluminum Chloride: Alteration of Cyp19a1, Pcna, Puma, and Map1lc3b genes Expression. Toxicology 11 34958889
2020 miR-326 down-regulate CYP19A1 expression and estradiol-17b production in buffalo granulosa cells through CREB and C/EBP-β. The Journal of steroid biochemistry and molecular biology 11 31996328
2018 Profile of CYP19A1 mRNA expression and aromatase activity during syncytialization of primary human villous trophoblast cells at term. Biochimie 11 29474975
2010 Intrauterine growth restriction alters hippocampal expression and chromatin structure of Cyp19a1 variants. Systems biology in reproductive medicine 11 20662593
2022 Association of CYP19A1 Gene, Plasma Zinc, and Urinary Zinc with the Risk of Type 2 Diabetes Mellitus in a Chinese Population. Biological trace element research 10 36441497
2020 Genetic Variations of CYP19A1 Gene and Stroke Susceptibility: A Case-Control Study in the Chinese Han Population. Journal of cardiovascular pharmacology 10 31895872
2020 Altered expression of CYP17A1 and CYP19A1 in undescended testes of dogs with unilateral cryptorchidism. Animal genetics 10 32657440
2015 Estrogen receptor alpha (Esr1) regulates aromatase (Cyp19a1) expression in the mouse brain. Neuro endocrinology letters 10 26071589
2014 Gene variations in oestrogen pathways, CYP19A1, daily 17β-estradiol and mammographic density phenotypes in premenopausal women. Breast cancer research : BCR 10 25522654
2013 CYP19A1 gene polymorphisms and risk of lung cancer. The Journal of international medical research 10 23669293

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