Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues

Means, Gary D.; Kilgore, Michael W.; Mahendroo, Mala S.; Mendelson, Carole R.; Simpson, Evan R.

doi:10.1210/mend-5-12-2005

Cited by 258Estrogen and related hormone effectsGenomics and Chromatin DynamicsOvarian function and disorders

Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues

Means, Gary D., Kilgore, Michael W., Mahendroo, Mala S., Mendelson, Carole R., Simpson, Evan R.·1991·Molecular Endocrinology

DOI 10.1210/mend-5-12-2005

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Abstract

The formation of estrogens from C19 steroids is catalyzed by a specific form of cytochrome P450, aromatase cytochrome P450 (P450AROM; the product of the CYP19 gene). Previous studies have demonstrated that aromatase activity in human adipose and ovarian granulosa cells is subject to complex multifactorial regulation and that changes in activity are correlated with changes in the levels of mRNA encoding P450AROM. We have previously isolated the human CYP19 gene. Two unique untranslated first exons (exons I.1 and I.2) have been identified in mRNA specific for P450AROM in human placenta. Although the proportion of transcripts encoding exon I.2 is very small, genomic clones encoding the sequences of both exons I.1 and I.2 have recently been isolated. The corpus luteum of human ovary differs in that promoters I.1 and I.2 are completely inactive. Sequence analysis of the DNA immediately 5' of exon II (which contains the start site of translation) demonstrates the presence of a TATAA sequence beginning 149 basepairs 5' of the ATG initiation codon identified in placental exon II. Using a combination of primer extension and S1 nuclease protection analysis, it appears that the initiation site of ovarian P450AROM transcripts aligns 26 basepairs down-stream of the sequence TATAA. It appears, therefore, that the expression of P450AROM-specific mRNA in corpus luteum is regulated by an additional promoter (promoter II), which is located just 5' of exon II. Consistent with these observations, Northern analysis of poly(A)+ RNA isolated from placenta and corpus luteum demonstrates that the major promoter of placental P450AROM is promoter I.1, while the major promoter in the corpus luteum is promoter II.(ABSTRACT TRUNCATED AT 250 WORDS)

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Three Different Promoters Control Expression of the Aromatase Cytochrome P450 Gene (Cyp19) in Mouse Gonads and Brain1
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Exon-specific northern analysis and rapid amplification of cDNA ends (RACE) reveal that the proximal promoter II (PII) is responsible for aromatase cytochrome P450 (CYP19) expression in human ovary
Jenkins, C. M., Michael, D., Mahendroo, M., & Simpson, E. R. (1993) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(93)90227-b · Cited by 71 · see citing works
Self-citation
Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta
Mahendroo, M. S., Means, G. D., Mendelson, C. R., & Simpson, E. R. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99159-3 · Cited by 175 · see citing works
Self-citation
Regulation of human aromatase cytochrome P450 gene expression
Simpson, E. R., Kilgore, M. W., Mahendroo, M., Means, G. D., Corbin, C. J., & Mendelson, C. R. (1992) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(92)90320-i · Cited by 14 · see citing works
Self-citation
Tissue-specific promoters regulate aromatase cytochrome P450 expression
Simpson, E. R., Mahendroo, M., Means, G., Kilgore, M. W., Corbin, C. J., & Mendelson, C. R. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.2.317 · Cited by 47 · see citing works
Self-citation
Regulation of Aromatase Expression in the Ovary and Placenta: a Comparison Between Two Species
Hinshelwood, M. M., Michael, M. D., Sun, T., & Simpson, E. R. (1997) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(96)00227-0 · Cited by 12 · see citing works
Self-citation

Authors: Means, G. D., Kilgore, M. W., Mahendroo, M. S., Mendelson, C. R., & Simpson, E. R.
Affiliations: The University of Texas Southwestern Medical Center (US)
ORCID: Mahendroo, Mala S.
Mendelson, Carole R.
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 1991-12
Volume: 5
Issue: 12
Pages: 2005-2013
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/mend-5-12-2005
OpenAlex: W2095719571
Cited by: 258
References: 40
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 11 · 2013: 5 · 2012: 2
FWCI: 5.56
Type: journal article
Language: en
Open access: closed
Locations: Molecular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AM-31206)
National Institute on Aging (AG-08174)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007190, 5-T32 HD07190)
Army Research Office
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Keywords: aromatase, P450arom, tissue-specific promoters, promoter analysis, corpus luteum, placenta, granulosa cells, translation initiation sites, estrogen synthesis, gene expression regulation
MeSH terms: Amino Acid Sequence, Aromatase, Base Sequence, DNA, Exons, Female, Fetus, Humans, Molecular Sequence Data, Ovary, Placenta, Pregnancy, Promoter Regions, Genetic, RNA, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Gene Expression, Polymerase Chain Reaction, TATA Box

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Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues

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