120287-85-6SBNPWPIBESPSIF-MHWMIDJBSA-NSBNPWPIBESPSIF-MHWMIDJBSA-N
CetrorelixCET
D-Alaninamide, N-acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-L-tyrosyl-N5-(aminocarbonyl)-D-ornithyl-L-leucyl-L-arginyl-L-prolyl-
DTXSID7040996308067-66-5Interleukin-6IL-6
DTXSID6041050PCO:0000008PCOpopulation growth rate2WIKIdecreasedProgesterone,estrogen,melatonin,Letrozole2019-10-03T11:39:392019-10-03T11:39:39glucocorticoids2019-10-03T12:06:122019-10-03T12:06:12Cetrorelix2019-10-03T12:09:442019-10-03T12:09:44Interleukin-6 2019-10-03T12:28:202019-10-03T12:28:20WikiUser_6ApacheUserfishAntagonism,LH receptorAntagonism,LH receptorMolecularAOPWiki2019-10-03T11:03:402019-10-03T11:03:40Reduction, Progesterone synthesisReduction, Progesterone synthesisCellularAOPWiki2019-10-03T11:04:492019-10-03T11:04:49Reduction, Plasma progesterone concentration Reduction, Plasma progesterone concentration TissueAOPWiki2019-10-03T11:06:552019-10-03T11:06:55Reduction, progesterone uptake, decresed maturation Reduction, progesterone uptake, decresed maturation CellularAOPWiki2019-10-03T11:09:182019-10-03T11:09:18Impaired ovulationImpaired ovulationOrganAOPWiki2019-10-03T11:10:162019-10-03T11:10:16Decrease of egg production and cummulative fecundityDecrease of egg production and cummulative fecundityIndividualAOPWiki2019-10-03T11:13:262019-10-03T11:13:26Decline, Population trajectoryDecline, Population trajectoryPopulationAOPWiki2016-11-29T18:41:262016-12-03T16:37:51
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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b430ba193d8>AOPWiki2019-10-03T11:17:392019-10-03T11:17:39Luteinizing hormone receptor antagonism leading to reproductive dysfunctionLuteinizing hormone receptor antagonismBrendan Ferreri-HanberryBY-SA2.0<p>This AOP is designed to detect changes in cumulative fecundity and egg production resulted from the inhibition of LHR by its antagonisms. Alteration of fecundity and ovulation in fish is the critical endpoint for reproductive toxicity caused by endocrine disrupting chemicals. This endpoint is essential and useful for screening of the potential endocrine disrupting chemicals and/or risk assessment. Therefore, this AOP can be applied to the prediction of reproductive toxicity caused by the inhibition of LHR.</p>
<p>This AOP describes an adverse outcome that results from the Luteinizing hormone (LH) receptor antagonism leading to reproductive dysfunction in female fish. Luteinizing hormone (LH) is glycoprotein hormones, called gonadotropins, that control gonadal functions. Gonadotropins exert their action through gonadotropin receptors, the LH receptor. In many species, LHR is primarily expressed in reproductive organs and function coordinately to control steroidogenesis and ovulation. It is well known that in teleosts, LHR is expressed primarily in the theca and granulosa cells of preovulatory ovarian follicles. LH regulates the expression of a variety of genes essential for ovulation, such as genes that code for steroidogenic enzymes (CYP11A1) which convert from cholesterol to pregnelone resulting the synthesis of progesterone. It is well organized that the luteinizing hormone triggers ovulation through progesterone binding to the progesterone receptor. The nuclear progesterone receptor, which is a member of the nuclear receptor transcription factor superfamily, has been suggested as an essential factor for LH-dependent ovulation in fish. In conclusion, LHR inhibition leads to a reduction of the synthesis of Progesterone, which is indispensable for ovulation and fertility in fish.</p>
<p><strong>Acknowledgements</strong>: This research was supported by the National Research Council of Science & Technology(NST) grant by the Korea government (MSIP) (No. CAP-17-01-KIST Europe)</p>
adjacentModerateModerateadjacentModerateHighadjacentModerateHighadjacentHighHighadjacentModerateHighadjacentHighHighHighFemaleNot Specified3 to < 6 monthsModerate<table border="1" cellpadding="0" cellspacing="0" style="width:841px">
<tbody>
<tr>
<td colspan="2" style="height:17px; width:463px">
<p><strong><u>To do</u></strong></p>
</td>
<td style="height:17px; width:97px">
<p><strong><u>Expected duration</u></strong></p>
</td>
</tr>
<tr>
<td rowspan="2" style="height:16px; width:168px">
<p>Building the AOP frame</p>
</td>
<td style="height:16px; width:294px">
<p>Development of KEs</p>
</td>
<td style="height:16px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Production of experimental data</p>
</td>
<td style="height:17px; width:97px">
<p>18 month</p>
</td>
</tr>
<tr>
<td rowspan="5" style="height:16px; width:168px">
<p>Overall assessment of the AOP</p>
</td>
<td style="height:16px; width:294px">
<p>Biological domain of applicability</p>
</td>
<td style="height:16px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Essentiality of all KEs</p>
</td>
<td style="height:17px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:16px; width:294px">
<p>Evidence supporting all KERs</p>
</td>
<td style="height:16px; width:97px">
<p>5 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Quantitative WoE considerations</p>
</td>
<td style="height:17px; width:97px">
<p>5 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Quantitative understanding for each KER</p>
</td>
<td style="height:17px; width:97px">
<p>6 month</p>
</td>
</tr>
</tbody>
</table>
Not SpecifiedModerateHighModerate<ol>
<li>Control of ovulation in mice by progesterone receptor-regulated gene networks Molecular Human Reproduction, Vol.15, No.12 pp. 821–828, 2009</li>
<li>Peroxisome Proliferator-Activated Receptor γ Is a Target of Progesterone Regulation in the Preovulatory Follicles and Controls Ovulation in Mice MOLECULAR AND CELLULAR BIOLOGY, Mar. 2008, p. 1770–178</li>
<li>Discovery of BAY-298 and BAY-899: Tetrahydro-1,6-naphthyridine-Based, Potent, and Selective Antagonists of the Luteinizing Hormone Receptor Which Reduce Sex Hormone Levels in Vivo J. Med. Chem. 2019, 62, 22, 10321-10341</li>
<li>Control of ovulation in mice by progesterone receptor-regulated gene networks Molecular Human Reproduction, Vol.15, No.12 pp. 821–828, 2009</li>
<li>Peroxisome Proliferator-Activated Receptor γ Is a Target of Progesterone Regulation in the Preovulatory Follicles and Controls Ovulation in Mice MOLECULAR AND CELLULAR BIOLOGY, Mar. 2008, p. 1770–178</li>
<li>A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS) Journal of the Turkish German Gynecology Association 15(4):250-1</li>
<li>Perspectives on fish gonadotropins and their receptors. Gen Comp Endocrinol 165: 412–437</li>
<li>Structural aspects of luteinizing hormone action. In: Ascoli M editor. Luteinizing hormone action and receptors. Boca Raton, Florida: CRC Press. 173–198.</li>
<li>Hormones of the adenohypophesis. The gonadotropins and thyrotropin (and related placental hormones). In: The Biochemistry of the Polypeptide Hormones. New York: John Wiley and Sons. 147–183.</li>
<li>Regulation of oocyte maturation in fish. Develop Growth Differ 50: 195–219.</li>
<li>Regulation of fish gonadotropins. Int Rev Cytol 225: 131–185.</li>
<li>Novel pathways in gonadotropin receptor signaling and biased agonism. Rev Endocr Metab Disord 12: 259–27</li>
<li>Regulation of oocyte maturation in fish. In: Sherwood NM, Hew CL, editors. Fish physiology. New York: Academic Press. 393–439.</li>
<li>Gene knockout of nuclear progesterone receptor provides insights into the regulation of ovulation by Lsignaling in zebrafish. Sci. Rep. 6, 28545–28545</li>
<li>Perspectives on fish gonadotropins and their receptors. Gen Comp Endocrinol 165: 412–437</li>
<li>Structural aspects of luteinizing hormone action. In: Ascoli M editor. Luteinizing hormone action and receptors. Boca Raton, Florida: CRC Press. 173–198.</li>
<li>Hormones of the adenohypophesis. The gonadotropins and thyrotropin (and related placental hormones). In: The Biochemistry of the Polypeptide Hormones. New York: John Wiley and Sons. 147–183.</li>
<li>Regulation of oocyte maturation in fish. Develop Growth Differ 50: 195–219.</li>
<li>Regulation of fish gonadotropins. Int Rev Cytol 225: 131–185.</li>
<li>Novel pathways in gonadotropin receptor signaling and biased agonism. Rev Endocr Metab Disord 12: 259–27</li>
<li>Regulation of oocyte maturation in fish. In: Sherwood NM, Hew CL, editors. Fish physiology. New York: Academic Press. 393–439.</li>
<li>Gene knockout of nuclear progesterone receptor provides insights into the regulation of ovulation by Lsignaling in zebrafish. Sci. Rep. 6, 28545–28545</li>
</ol>
AOPWiki2019-10-03T10:43:372023-09-25T16:27:01