1912-24-9 MXWJVTOOROXGIU-UHFFFAOYSA-N MXWJVTOOROXGIU-UHFFFAOYSA-N Atrazine 1,3,5-Triazine-2,4-diamine, 6-chloro-N-ethyl-N'-(1-methylethyl)- 1,3,5-Triazine-2,4-diamine, 6-chloro-N2-ethyl-N4-(1-methylethyl)- 1-Chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine 2-Chloro-4-(ethylamino)-6-(2-propylamino)-s-triazine 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine 2-Chloro-4-(ethylamino)-6-(isopropylamino)triazine 2-Chloro-4-ethylamineisopropylamine-s-triazine 2-Chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine 2-Chloro-4-ethylamino-6-isopropylamino-s-triazine 2-Ethylamino-4-isopropylamino-6-chloro-s-triazine 6-Chloro-4-(ethylamino)-2-(isopropylamino)-s-triazine 6-Chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine AAtrex Nine-O Akticon Aktikon Aktikon PK Aktinit A Aktinit PK Argezin Atragranz Atranex Atranex 80WP Atraphyt Atrataf Atrazin atrazina Azoprim Chromozin Farmozine Gesamprim Gesaprim Gesaprim 50 Gesaprim 500 Gesaprim L Herbatoxol Hungazin Hungazin PK NSC 163046 Nu-Trazine Oleogesaprim Oleogesaprim 200 Primatol A Primoleo Radazin Radazin T s-Triazine, 2-chloro-4-(ethylamino)-6-(isopropylamino)- Triazine A 1294 Zealin L Zeazine DTXSID9020112 D007987 MESH Gonadotropin Releasing Hormone CHEBI:81568 CHEBI Luteinizing hormone CHEBI:50114 CHEBI estrogen CL:0000439 CL prolactin secreting cell D000236 MESH Adenoma GO:0046879 GO hormone secretion MP:0009006 MP prolonged estrous cycle MP:0009017 MP prolonged estrus MP:0001928 MP abnormal ovulation D006965 MESH hyperplasia D006984 MESH hypertrophy HP:0002893 HP Pituitary adenoma 2 WIKI decreased 1 WIKI increased 9 WIKI disrupted atrazine 2016-11-29T18:42:27 2016-11-29T18:42:27 WikiUser_17 mammals 10116 NCBI SD rat Decreased, GnRH pulsatility/release in hypothalamus Cellular CL:0011111 CL gonadotropin releasing neuron AOPWiki 2016-11-29T18:41:29 2017-09-16T10:17:11 Decreased, LH Surge from anterior pituitary Cellular AOPWiki 2016-11-29T18:41:29 2016-12-03T16:37:53 prolonged, estrus cycle Individual <p><em>The estrus cycle is a coordinated series of changes that results in fertility in mammals. &nbsp;Changes to the uterus and vagina are coordinated through hormone signaling, including Progesterone, Estradiol, Luteinizing Hormone, and Follicle-Stimulating Hormone in order to progress through metestrus, diestrus, proestrus, and estrous phases &nbsp;over a period of 4-5 days in rodents (Miller and Takahashi 2014; Swift et al. 2024). &nbsp;In proestrus, increased estradiol levels occur, and physiological changes include ovarian follicle development and the thickening of the uterine wall in preparation for potential pregnancy. &nbsp;In estrus, a surge in luteinizing hormone levels occur, and ovulation of the mature egg. &nbsp;Metestrus is a short transition between estrus and diestrus, features an increase in progesterone levels, and development of the corpus luteum begins in preparation for pregnancy. &nbsp;Diestrus includes continued high levels of progesterone and further development of the corpus luteum; if pregnancy does not occur the corpus luteum regresses and resetting of the cycle occurs. &nbsp;Prolonged estrous occurs when the normal estrus cycle progression has been disrupted.</em></p> <p><br /> <em>Length of phases of the estrus cycle (modified from data/format from Ajayi and Akhigbe 2020):</em></p> <table cellspacing="0" class="MsoTableGrid" style="border-collapse:collapse; border:none"> <tbody> <tr> <td style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:1px solid black; vertical-align:top; width:102px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Phase</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:1px solid black; vertical-align:top; width:150px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Length in Rats</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:1px solid black; vertical-align:top; width:180px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Length in Mice</em></span></span></p> </td> </tr> <tr> <td style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; vertical-align:top; width:102px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Proestrus</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:150px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>14 hours</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:180px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>&lt;24 hours</em></span></span></p> </td> </tr> <tr> <td style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; vertical-align:top; width:102px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Estrus</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:150px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>24-48 hours</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:180px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>12-48 hours</em></span></span></p> </td> </tr> <tr> <td style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; vertical-align:top; width:102px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Mestestrus</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:150px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>6-8 hours</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:180px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>8-24 hours</em></span></span></p> </td> </tr> <tr> <td style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; vertical-align:top; width:102px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>Diestrus</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:150px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>48-72 hours</em></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; vertical-align:top; width:180px"> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><em>48-72 hours</em></span></span></p> </td> </tr> </tbody> </table> <p>&nbsp;</p> <p><em>The phases of the estrus cycles are determined by anatomical changes to the vagina and uterus, as well as vaginal smear/cytology (Laffan et al. 2018; Ajayi and Akhigbe 2020).&nbsp;</em></p> <p><br /> <em>Analysis of hormone levels can also be performed but are more labor intensive, more stressful to animals, and less definitive than physical examination.</em><br /> &nbsp;</p> <p><em>Life Stage: Adult, reproductively mature and juveniles.</em></p> <p><br /> <em>Sex: Applies to females.</em></p> <p><br /> <em>Taxonomic: Primarily studied in laboratory rodents. &nbsp;Plausible for most mammals due to shared reproductive physiology and hormones. &nbsp;Primates have menstrual cycles as the lining of the uterus is shed rather than being reabsorbed.</em><br /> &nbsp;</p> High Female Moderate Adult, reproductively mature High <p><em>Ajayi, A.F. and Akhigbe, R.E. &nbsp;2020. &nbsp;Staging of the estrous cycle and induction of estrus in experimental rodents: an update. &nbsp;Fertility Research and Practice 6: 5.</em></p> <p><br /> <em>Laffan, S.B., Lorraine M. Posobiec, L.M., Jenny E. Uhl, J.E., and Vidal, J.D. &nbsp;2018. &nbsp;Species Comparison of Postnatal Development of the Female Reproductive System. Birth Defects Research 110(3): 163-189.</em></p> <p><br /> <em>Miller, B.H. and Takahashi, J.S. &nbsp;2014. &nbsp;Central circadian control of female reproductive function. &nbsp;Frontiers in Endocrinology 4(1): 195.</em></p> <p><br /> <em>Swift, K.M., Gary, N.C., and Urbanczyk, P.J. &nbsp;2024. &nbsp;On the basis of sex and sleep: the influence of the estrous cycle and sex on sleep-wake behavior. &nbsp;Frontiers in Neuroscience 18:1426189.</em></p> <p><br /> <em>NOTE: Italics indicate edits from John Frisch October 2025. &nbsp;A full list of updates can be found in the Change Log on the View History page.</em><br /> &nbsp;</p> AOPWiki 2016-11-29T18:41:29 2025-10-03T11:27:16 interruption, Ovulation Individual AOPWiki 2016-11-29T18:41:29 2016-12-03T16:37:53 Increased, circulating estrogen levels Organ AOPWiki 2016-11-29T18:41:29 2016-12-03T16:37:53 Increased, lactotroph hyperplasia and hypertrophy Cellular CL:0000439 CL prolactin secreting cell AOPWiki 2016-11-29T18:41:29 2017-09-16T10:17:13 Increased, adenomas (pituitary) Tissue UBERON:0000007 UBERON pituitary gland AOPWiki 2016-11-29T18:41:29 2017-09-16T10:17:14 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 AOPWiki 2016-11-29T18:41:36 2016-12-03T16:38:03 GnRH pulse disruption and pituitary tumors Charles Wood <p>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)</p> BY-SA 1.0 <p>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.</p> adjacent Not Specified High adjacent Not Specified High adjacent Not Specified High adjacent Not Specified High non-adjacent Not Specified High non-adjacent Not Specified High non-adjacent Not Specified High High Female High Not Specified <p>1. O&#39;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.</p> AOPWiki 2016-11-29T18:41:17 2026-01-11T16:56:07