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Aromatase expression in endometriosis.
Abstract
The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.
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“Local E2 levels are increased in endometriosis due to upregulation of the aromatase gene CYP19A1 [34] and reduction of 17-hydroxysteroid dehydrogenase type 2 (17HSD2), which normally (induced by P4) converts E2 to the less potent estrone [35, 36].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [34]
In the citing paper
“the first report of aromatase upregulation used 17 lesion samples and 7 control endometrial samples (Noble et al., 1996), while that on ERα used 9 and 11 samples, respectively (Brandenberger et al., 1999).”
From Progressively diminished estrogen signaling concordant with increased fibrosis in ectopic endometrium (2025) · cites this paper as Noble et al., 1996
In the citing paper
“The products of some of these steroidogenic genes that catalyze the formation of estradiol from cholesterol, namely StAR, P450arom (CYP19A1), and HSD17B1 were demonstrated in stromal cells of endometriotic tissue (10 -13).”
From Prostaglandin E2 Via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis (2009) · cites this paper as [12]
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Oral contraceptives for endometriosis-associated pain
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Akad, M., Socolov, R. V., Covali, R. A., Catalina Daniela, S. T. A. N., Crauciuc, E., Popovici, D., Stan, C. I., Akad, F., & Socolov, D. G. (2022) · MAEDICA – a Journal of Clinical Medicine · doi:10.26574/maedica.2022.17.3.557 · Cited by 3
Etiologies of endometriosis and model systems: is there a risk of a tunnel vision?
Manavalan, M. A., Babtain, M., Weessies, M., Nap, A. W., Verdurmen, W. P. R., Taurin, S., Sater, M. S., & Brock, R. E. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1675051 · Cited by 3
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Endometriosis and adenomyosis – a shared pathophysiology
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The Environment and Reproduction: Endocrine Disruption, Reproductive Impairment, and Epigenetics
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Endometriosis: a uterine disease with extrauterine lesions?
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LEYENDECKER, G., & Wildt, L. (2011) · Springer eBooks · doi:10.1007/978-3-642-15012-8_9 · Cited by 2
Pacheco, K. G. (2014) · Gynecology & Obstetrics · doi:10.4172/2161-0932.1000258 · Cited by 2
“Patients with endometriosis present an aberrant expression of estrogen and progesterone receptors and factors that interfere with angiogenesis [26-31].”
BackgroundPelvic Imaging in Reproductive Endocrinology
de Ziegler, D., Streuli, I., Santulli, P., & Chapron, C. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4557-2758-2.00035-4 · Cited by 2
Pelvic Imaging in Reproductive Endocrinology
de Ziegler, D., Fraisse, T., Millischer, A., & Chapron, C. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-4907-4.00033-4 · Cited by 2
Nowak, N. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-12324 · Cited by 2
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Aromatase et endométriose : mythe ou réalité ?
Colette, S., & Donnez, J. (2010) · Gynécologie Obstétrique & Fertilité · doi:10.1016/j.gyobfe.2010.03.014 · Cited by 2
Medikamentöse und konservative Therapie
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Hudson, T. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4377-2333-5.00162-0 · Cited by 1
Dislozierung basalen Endometriums
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Investigating endometriosis: symptoms, diagnosis and treatment
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The Implication of Angiogenesis in Endometriosis
Ilie, R., & Ilie, I. R. P. (2014) · Cited by 1
Current Treatment for Adenomyosis
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Koshiba, A., Mori, T., Ito, F., Tanaka, Y., Takaoka, O., Takahata, A., & Kitawaki, J. (2016) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.13153 · Cited by 1
de Ziegler, D., Fraisse, T., & Chapron, C. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511547287.007 · Cited by 1
Metadata
- Authors
- Noble, L. S., Simpson, E. R., Johns, A., & Bulun, S. E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Bulun, S E
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1996-01
- Volume
- 81
- Issue
- 1
- Pages
- 174-179
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2023838867
- Cited by
- 566
- References
- 10
- Citations by year
- 2025: 9 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 14 · 2020: 17 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 20 · 2015: 28 · 2014: 22 · 2013: 18 · 2012: 22
- FWCI
- 17.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R-37AG08174, R37AG008174)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometriosis, aromatase, P450arom, endometriotic implants, eutopic endometrium, estrogen synthesis, promoter usage, alternative splicing, tissue-specific gene expression, peritoneal endometriosis, aromatase mRNA expression
- MeSH terms
- Adult, Aromatase, Base Sequence, Endometriosis, Endometrium, Female, Humans, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger, Interleukin-6, Gene Expression Regulation, Enzymologic, Interleukin-11
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