API XML

Aop: 111

AOP Title

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Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)

Short name:

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Decreased AR activity- Leydig cell tumors

Graphical Representation

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Click to download graphical representation template

Authors

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Cancer AOP group. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (wood.charles@epa.gov)

Point of Contact

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Charles Wood   (email point of contact)

Contributors

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  • Charles Wood

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
Decreased, Androgen receptor activity December 03, 2016 16:37
Decreased, Testosterone binding to androgen receptor (hypothalamus) September 16, 2017 10:16
Increase, Hyperplasia (Leydig cells) September 16, 2017 10:16
Increase, Leydig cell tumors September 16, 2017 10:16
Increased, Luteinizing hormone (LH) September 16, 2017 10:16
Decreased, Androgen receptor activity leads to Decreased, Testosterone binding to androgen receptor (hypothalamus) December 03, 2016 16:37
Increase, Hyperplasia (Leydig cells) leads to Increase, Leydig cell tumors December 03, 2016 16:37
Decreased, Testosterone binding to androgen receptor (hypothalamus) leads to Increased, Luteinizing hormone (LH) December 03, 2016 16:38
Increased, Luteinizing hormone (LH) leads to Increase, Hyperplasia (Leydig cells) December 03, 2016 16:38

Abstract

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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.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 742 Decreased, Androgen receptor activity Decreased, Androgen receptor activity
2 KE 743 Decreased, Testosterone binding to androgen receptor (hypothalamus) Decreased, Testosterone binding to androgen receptor (hypothalamus)
3 KE 744 Increase, Hyperplasia (Leydig cells) Increase, Hyperplasia (Leydig cells)
4 KE 754 Increased, Luteinizing hormone (LH) Increased, Luteinizing hormone (LH)
5 AO 745 Increase, Leydig cell tumors Increase, Leydig cell tumors

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Decreased, Androgen receptor activity leads to Decreased, Testosterone binding to androgen receptor (hypothalamus) adjacent
Increase, Hyperplasia (Leydig cells) leads to Increase, Leydig cell tumors adjacent
Decreased, Testosterone binding to androgen receptor (hypothalamus) leads to Increased, Luteinizing hormone (LH) adjacent
Increased, Luteinizing hormone (LH) leads to Increase, Hyperplasia (Leydig cells) adjacent

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Rattus norvegicus Rattus norvegicus NCBI

Sex Applicability

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Sex Evidence
Male

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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Cook, J. C., Klinefelter, G. R., Hardisty, J. F., Sharpe, R. M., & Foster, P. M. (1999). Rodent Leydig cell tumorigenesis: a review of the physiology, pathology, mechanisms, and relevance to humans. Crit Rev Toxicol, 29(2), 169-261. doi: 10.1080/10408449991349203