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Aromatase in endometriosis and uterine leiomyomata
Abstract
Endometrial tissue from uterine disease-free women does not exhibit aromatase activity. In contrast, aromatase enzyme activity and mRNA levels are readily detectable in endometriosis. PGE2 stimulates both aromatase expression and activity in endometriotic stromal cells via promoter II region of the aromatase gene. This results in local production of estradiol, which induces PGE2 formation and establishes a positive feedback cycle. This mechanism seems to contribute to continuous production of estradiol and PGE2. Aromatase mRNA levels and enzyme activity are also present in uterine leiomyomata that are estrogen-dependent benign tumors of the myometrium. Successful treatment of endometriosis and uterine leiomyomata using aromatase inhibitors by recent pilot trials underscores the clinical significance of these molecular studies.
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“The oestrogen can be further produced in the endometrial lesions by aromatase activity [14].”
From 5-Year data analysis of patients following abdominal wall endometrioma surgery (2014) · cites this paper as [14]
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Šmuc, T., Hevir, N., Ribič-Pucelj, M., Husen, B., Thole, H., & Rižner, T. L. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.07.020 · Cited by 101
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ResultAromatase inhibitors for the treatment of endometriosis
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Self-citationZhang, H., Niu, Y., Feng, J., Guo, H., Ye, X., & Cui, H. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.01.028 · Cited by 101
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BackgroundProgestins Activate the AKT Pathway in Leiomyoma Cells and Promote Survival
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“Interestingly, endometriotic lesions have been shown to produce high levels of E2 (15), and there is evidence that MCs”
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Myomectomy Decreases Abnormal Uterine Peristalsis and Increases Pregnancy Rate
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“Therefore, in there women AIs may only be justified when GnRH analogs fail to control the disease through the elimination of estradiol secreted by the ovary [18], probably due to the presence of significant estradiol production that continues in the adipose tissue, skin, and endometriotic implant per se during the GnR…”
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“This may result in serum levels of estradiol, which are capable of causing endometrial hyperplasia or even endometrial carcinoma [69].”
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5-Year data analysis of patients following abdominal wall endometrioma surgery
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“pELs produce oestrogen locally [79–82].”
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“Aromatase is overexpressed in uterine fibroids compared with normal myometrium, suggesting an interaction between androgen and estrogen in uterine fibroids [42].”
BackgroundCYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women
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“org uterine leiomyomata (Bulun et al. 2005), and adrenocortical carcinoma cell lines (Watanabe et al.”
BackgroundKoltsova, A. S., Efimova, O. A., & Pendina, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065752 · Cited by 31
Hur, S. E., Lee, S., Lee, J. Y., Moon, H. S., Kim, H. L., & Chung, H. W. (2007) · Journal of Human Genetics · doi:10.1007/s10038-007-0174-x · Cited by 26
Insulin-Like Growth Factor I Enhances the Expression of Aromatase P450 by Inhibiting Autophagy
Zhang, B., Shozu, M., Okada, M., Ishikawa, H., Kasai, T., Murakami, K., Nomura, K., Harada, N., & Inoue, M. (2010) · Endocrinology · doi:10.1210/en.2010-0294 · Cited by 24
Pohl, O., Bestel, E., & Gotteland, J. (2014) · Reproductive Sciences · doi:10.1177/1933719114522526 · Cited by 24
How can macroscopically normal peritoneum contribute to the pathogenesis of endometriosis?
Fassbender, A., Overbergh, L., Verdrengh, E., Kyama, C., Vodolazakaia, A., Bokor, A., Meuleman, C., Peeraer, K., Tomassetti, C., Waelkens, E., et al. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.06.034 · Cited by 25
“38 [0–17]) 1.”
Kumru, S., Yildiz, A. A., Yılmaz, B., Sandal, S., & Gürateş, B. (2007) · Gynecological Endocrinology · doi:10.1080/09513590701557119 · Cited by 22
“AIs have recently been used for the treatment of endometriosis [6] and uterine leiomyomata [7] in women of reproductive age.”
MethodWise, L. A., & Laughlin-Tommaso, S. K. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-384978-6.00019-4 · Cited by 21
Prevalence of deep and ovarian endometriosis in early pregnancy: ultrasound diagnostic study
Bean, E., Naftalin, J., Horne, A. W., Sarıdoğan, E., Cutner, A. S., & Jurkovic, D. (2021) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.24756 · Cited by 22
de Abreu, L. G., Romão, G. S., dos Reis, R. M., Ferriani, R. A., de Sá, M. F. S., & de Moura, M. D. (2006) · Gynecological Endocrinology · doi:10.1080/09513590600902937 · Cited by 20
Maclaran, K., Agarwal, N., & Odejinmi, F. (2014) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2014.05.013 · Cited by 21
Medical Therapies for Chronic Menorrhagia
Nelson, A. L., & Teal, S. B. (2007) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000259228.70277.6f · Cited by 19
“Their effectiveness in small-scale trials treating endometriosis and uterine leiomyomata (76,77) suggest that direct suppression of estrogen production could have significant effect in suppressing endometrial proliferation in women with menorrhagia.”
BackgroundKhazaei, M., Montaseri, A., & Casper, R. F. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.02.090 · Cited by 18
Unveiling the Pathogenesis of Adenomyosis through Animal Models
Wang, X., Benagiano, G., Liu, X., & Guo, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11061744 · Cited by 19
Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas
Chuang, T., Gao, J., Quintanilla, D., McSwiggin, H., Boos, D., Yan, W., & Khorram, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043742 · Cited by 18
“The growth of leiomyomas is dependent on estrogen [4] and early studies demonstrated that the expression level of CYP19A1, or aromatase, which is a member of the cytochrome P450 superfamily and converts androgens to estrogens [68], is higher in leiomyomas [101] and this increase is more pronounced in African American…”
ResultSimsa, P., Mihalyi, A., Kyama, C. M., Mwenda, J. M., Fülöp, V., & D’Hooghe, T. M. (2007) · Women s Health · doi:10.2217/17455057.3.5.617 · Cited by 17
“The genetic background and regulation of the aromatase gene (CYP19A1) is well known [2,4,5].”
BackgroundSmall primary adenocarcinoma in adenomyosis with nodal metastasis: a case report
Puppa, G., Shozu, M., Perin, T., Nomura, K., Gloghini, A., Campagnutta, E., & Canzonieri, V. (2007) · BMC Cancer · doi:10.1186/1471-2407-7-103 · Cited by 17
“Endometriosis and leiomyomas constitute two added sources of aberrant estrogen biosynthesis, primarily by aromatase enzymatic activity, promoting their selfstimulation [15,16].”
BackgroundSkin endometriosis: A case report and review of the literature
Matei, A.-M., Draghici‑Ionescu, A.-M., Cioplea, M., Zurac, S., Boda, D., Serban, I., Caruntu, C., Ilie, M., & Gyula, L. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.9964 · Cited by 16
Yu, C., Li, Y., Chen, H., Yang, S., & Xie, G. (2008) · Food and Chemical Toxicology · doi:10.1016/j.fct.2008.09.045 · Cited by 16
Li, Z., Liu, H., He, Z., Zhang, G., & Lang, J. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.07.018 · Cited by 16
Conformational selection is present in ligand binding to cytochrome P450 19A1 lipoprotein nanodiscs
Zárate-Pérez, F., & Hackett, J. C. (2020) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2020.111120 · Cited by 16
Thoracic and diaphragmatic endometriosis: An overview of diagnosis and surgical treatment
McKee, D. C., Mansour, T., & Wasson, M. N. (2022) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000792 · Cited by 16
Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation
McCallion, A., Sisnett, D. J., Zutautas, K. B., Hayati, D., Spiess, K. G., Aleksieva, S., Lingegowda, H., Koti, M., & Tayade, C. (2022) · Exploration of Immunology · doi:10.37349/ei.2022.00062 · Cited by 16
“This is compounded by estradiol production resulting from aromatase activity in endometriotic tissue, as CYP19 expression is significantly increased in endometriosis lesions compared to healthy endometrium [109, 110].”
BackgroundPollakisuria in a dwarf goat due to pathologic enlargement of the uterus
Pfister, P., Geissbuehler, U., Wiener, D. J., Hirsbrunner, G., & Kaufmann, C. (2007) · Veterinary Quarterly · doi:10.1080/01652176.2007.9695234 · Cited by 15
“PGE is known to be upregulating the enzyme aromatase P450 in a positive feed-back mechanism (4).”
BackgroundSapmaz, T., Coskun, G., Saker, D., Pence, H. H., Keles, P., Hayretdag, C., Kuras, S., Topkaraoglu, S., Erdem, E., Efendic, F., et al. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153951 · Cited by 15
Fetal safety profile of aromatase inhibitors: Animal data
Tiboni, G. M., & Ponzano, A. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.09.016 · Cited by 16
The Rising Phoenix-Progesterone as the Main Target of the Medical Therapy for Leiomyoma
Chill, H. H., Safrai, M., Salzman, A. R., & Shushan, A. (2017) · BioMed Research International · doi:10.1155/2017/4705164 · Cited by 14
Yang, Y., Liu, J., & Xu, W. (2022) · Acta Biochimica Polonica · doi:10.18388/abp.2020_5722 · Cited by 13
“There was evidence that cardio-metabolic risk, insulin resistance, and weight gain are associated with PCOS (Ardawi & Rouzi, 2005; Bulun et al., 2005; Rakha et al., 2012).”
BackgroundZhang, Y., Shaukat, A., Zhang, H., Yang, Y.-F., Li, H., Li, G., Liu, Y., Liang, C., Kang, J., Li, S.-C., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313150 · Cited by 12
“In ectopic endometrium, a higher level of ESR1, activated by ovarian and locally synthesized E 2 , leads to excessive proliferation of endometrial tissues [12,13].”
Metadata
- Authors
- Bulun, S. E., Imir, G., Utsunomiya, H., Thung, S., Gurates, B., Tamura, M., & Lin, Z.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Bulun, Serdar E.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 95
- Issue
- 1-5
- Pages
- 57-62
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2119512564
- Cited by
- 154
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 11 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 11 · 2013: 3 · 2012: 11
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046260, HD-38691, HD46260)
- 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 › Uterine Myomas and Treatments
- Keywords
- aromatase, endometriosis, uterine fibroids, prostaglandin E2, endometrial stromal cells, estradiol production, positive feedback loop, aromatase inhibitors, estrogen-dependent tumors
- MeSH terms
- Aromatase, Endometriosis, Estrogens, Female, Humans, Leiomyoma, Uterine Neoplasms, Uterus, Aromatase Inhibitors
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