Steroidogenic factor-1 and endometriosis
Abstract
Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE(2) induces the expression of the genes that encode these enzymes. Upon PGE(2) treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE(2) by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women.
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PGE2 activates PKA signaling via raising intracellular cAMP, which can enhance binding of SF-1 to promoters of steroidogenic genes and induce phosphorylation of CREB.
“PGE2 activates the protein kinase A (PKA) signaling pathway via raising the intracellular levels of cyclic adenosine 3′,5′-monophosphate (cAMP)12–14, which can enhance the binding of steroidogenic factor-1 (SF-1) to promoters of these steroidogenic genes15, and induce phosphorylation of the transcriptional activator cAMP-response element-binding protein (CREB)16.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [15]
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Self-citation
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Hormonal treatments for endometriosis: The endocrine background
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- Authors
- Bulun, S. E., Utsunomiya, H., Lin, Z., Yin, P., Cheng, Y.-H., Pavone, M. E., Tokunaga, H., Trukhacheva, E., Attar, E., Gurates, B., Milad, M. P., Confino, E., Su, E., Reierstad, S., & Xue, Q.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Bulun, Serdar E.
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 300
- Issue
- 1-2
- Pages
- 104-108
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2060023420
- Cited by
- 80
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 7
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- steroidogenic factor 1, SF-1, endometriosis, estradiol synthesis, aromatase, prostaglandin E2, steroidogenesis, promoter methylation, aromatase inhibitors, infertility, pelvic pain
- MeSH terms
- Endometriosis, Endometrium, Estradiol, Female, Humans, Inflammation, Transcription Factors, Dinoprostone, Steroidogenic Factor 1
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