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AOP: 165
Title
Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
Short name
Graphical Representation
Point of Contact
Contributors
- Charles Wood
- Evgeniia Kazymova
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
1.29 |
This AOP was last modified on May 26, 2024 20:39
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Decreased, Ovarian E2 | September 16, 2017 10:17 |
Suppression, Estrogen receptor (ER) activity | February 28, 2022 23:08 |
Increased, secretion of GnRH from hypothalamus | September 16, 2017 10:17 |
Increased, secrection of FSH from anterior pituitary | December 03, 2016 16:37 |
Increased, secretion of LH from anterior pituitary | December 03, 2016 16:37 |
Hyperplasia, ovarian stromal cells | September 16, 2017 10:17 |
Hyperplasia, ovarian epithelium | September 16, 2017 10:17 |
Promotion, ovarian adenomas | December 03, 2016 16:37 |
Promotion, ovarian granular cell tumors | December 03, 2016 16:37 |
Decrease, E2 blood concentrations at hypothalamus | September 16, 2017 10:17 |
Decreased, Ovarian E2 leads to Decrease, E2 blood concentrations at hypothalamus | December 03, 2016 16:38 |
Suppression, Estrogen receptor (ER) activity leads to Decrease, E2 blood concentrations at hypothalamus | December 03, 2016 16:38 |
Decrease, E2 blood concentrations at hypothalamus leads to Increased, secretion of GnRH from hypothalamus | December 03, 2016 16:38 |
Increased, secretion of GnRH from hypothalamus leads to Increased, secrection of FSH from anterior pituitary | December 03, 2016 16:38 |
Increased, secretion of GnRH from hypothalamus leads to Increased, secretion of LH from anterior pituitary | March 01, 2022 06:01 |
Increased, secrection of FSH from anterior pituitary leads to Hyperplasia, ovarian stromal cells | December 03, 2016 16:38 |
Increased, secrection of FSH from anterior pituitary leads to Hyperplasia, ovarian epithelium | December 03, 2016 16:38 |
Increased, secretion of LH from anterior pituitary leads to Hyperplasia, ovarian stromal cells | December 03, 2016 16:38 |
Hyperplasia, ovarian epithelium leads to Promotion, ovarian adenomas | December 03, 2016 16:38 |
Hyperplasia, ovarian stromal cells leads to Promotion, ovarian granular cell tumors | December 03, 2016 16:38 |
Tamoxifen | November 29, 2016 18:42 |
Raloxifene | November 29, 2016 18:42 |
Fulvestrant | November 29, 2016 18:42 |
Abstract
This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
KE | 1045 | Decreased, Ovarian E2 | Decreased, Ovarian E2 |
KE | 1046 | Suppression, Estrogen receptor (ER) activity | Suppression, Estrogen receptor (ER) activity |
KE | 1047 | Increased, secretion of GnRH from hypothalamus | Increased, secretion of GnRH from hypothalamus |
KE | 1049 | Increased, secrection of FSH from anterior pituitary | Increased, secrection of FSH from anterior pituitary |
KE | 1050 | Increased, secretion of LH from anterior pituitary | Increased, secretion of LH from anterior pituitary |
KE | 1051 | Hyperplasia, ovarian stromal cells | Hyperplasia, ovarian stromal cells |
KE | 1052 | Hyperplasia, ovarian epithelium | Hyperplasia, ovarian epithelium |
KE | 1056 | Decrease, E2 blood concentrations at hypothalamus | Decrease, E2 blood concentrations at hypothalamus |
AO | 1053 | Promotion, ovarian adenomas | Promotion, ovarian adenomas |
AO | 1054 | Promotion, ovarian granular cell tumors | Promotion, ovarian granular cell tumors |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Female | High |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
1. Capen, C. C. (2004). Mechanisms of hormone-mediated carcinogenesis of the ovary. Toxicologic pathology 32 Suppl 2, 1-5.
2. Cohen, I. R., Sims, M. L., Robbins, M. R., Lakshmanan, M. C., Francis, P. C., and Long, G. G. (2000). The reversible effects of raloxifene on luteinizing hormone levels and ovarian morphology in mice. Reproductive toxicology 14(1), 37-44.
3. Long, G. G., Cohen, I. R., Gries, C. L., Young, J. K., Francis, P. C., and Capen, C. C. (2001). Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator. Toxicologic pathology 29(6), 719-26.