API XML

Aop: 169

AOP Title

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GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.

Short name:

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GnRH pulse disruption and pituitary tumors

Graphical Representation

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Click to download graphical representation template

Authors

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Cancer AOP Workgroup. 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 Do not cite 1.29 Under Development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, GnRH pulsatility/release in hypothalamus September 16, 2017 10:17
Decreased, LH Surge from anterior pituitary December 03, 2016 16:37
prolonged, estrus December 03, 2016 16:37
interruption, Ovulation December 03, 2016 16:37
Increased, circulating estrogen levels December 03, 2016 16:37
Increased, lactotroph hyperplasia and hypertrophy September 16, 2017 10:17
Increased, adenomas (pituitary) September 16, 2017 10:17
Decreased, GnRH pulsatility/release in hypothalamus leads to Decreased, LH Surge from anterior pituitary December 03, 2016 16:38
Decreased, LH Surge from anterior pituitary leads to prolonged, estrus December 03, 2016 16:38
Decreased, LH Surge from anterior pituitary leads to interruption, Ovulation December 03, 2016 16:38
prolonged, estrus leads to Increased, circulating estrogen levels December 03, 2016 16:38
interruption, Ovulation leads to Increased, circulating estrogen levels December 03, 2016 16:38
Increased, circulating estrogen levels leads to Increased, lactotroph hyperplasia and hypertrophy December 03, 2016 16:38
Increased, lactotroph hyperplasia and hypertrophy leads to Increased, adenomas (pituitary) December 03, 2016 16:38
atrazine November 29, 2016 18:42

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 KE 1071 Decreased, GnRH pulsatility/release in hypothalamus Decreased, GnRH pulsatility/release in hypothalamus
2 KE 1072 Decreased, LH Surge from anterior pituitary Decreased, LH Surge from anterior pituitary
3 KE 1075 prolonged, estrus prolonged, estrus
4 KE 1074 interruption, Ovulation interruption, Ovulation
5 KE 1076 Increased, circulating estrogen levels Increased, circulating estrogen levels
6 KE 1081 Increased, lactotroph hyperplasia and hypertrophy Increased, lactotroph hyperplasia and hypertrophy
7 AO 1082 Increased, adenomas (pituitary) Increased, adenomas (pituitary)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Decreased, GnRH pulsatility/release in hypothalamus leads to Decreased, LH Surge from anterior pituitary adjacent High
Decreased, LH Surge from anterior pituitary leads to interruption, Ovulation adjacent High
prolonged, estrus leads to Increased, circulating estrogen levels adjacent High
Increased, circulating estrogen levels leads to Increased, lactotroph hyperplasia and hypertrophy adjacent High
Decreased, LH Surge from anterior pituitary leads to prolonged, estrus non-adjacent High
interruption, Ovulation leads to Increased, circulating estrogen levels non-adjacent High
Increased, lactotroph hyperplasia and hypertrophy leads to Increased, adenomas (pituitary) non-adjacent High

Network View

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Stressors

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Name Evidence Term
atrazine

Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
SD rat Rattus norvegicus High NCBI

Sex Applicability

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Sex Evidence
Female High

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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1. O'Connor, J. C., Davis, L. G., Frame, S. R., and Cook, J. C. (2000). Detection of dopaminergic modulators in a tier I screening battery for identifying endocrine-active compounds (EACs). Reproductive toxicology 14(3), 193-205.