Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling
Abstract Approximately half of U.S. women giving birth annually receive Pitocin, a synthetic form of oxytocin (OXT), yet the optimal dosing remains challenging due to significant individual variability in response. To address this, we developed a mathematical model examining the effects of five OXT...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Women's Health |
| Online Access: | https://doi.org/10.1038/s44294-025-00058-y |
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| _version_ | 1823861500017639424 |
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| author | Preeti Dubey Yingye Fang K. Lionel Tukei Shobhan Kuila Xinming Liu Annika Sahota Antonina I. Frolova Erin L. Reinl Manasi Malik Sarah K. England Princess I. Imoukhuede |
| author_facet | Preeti Dubey Yingye Fang K. Lionel Tukei Shobhan Kuila Xinming Liu Annika Sahota Antonina I. Frolova Erin L. Reinl Manasi Malik Sarah K. England Princess I. Imoukhuede |
| author_sort | Preeti Dubey |
| collection | DOAJ |
| description | Abstract Approximately half of U.S. women giving birth annually receive Pitocin, a synthetic form of oxytocin (OXT), yet the optimal dosing remains challenging due to significant individual variability in response. To address this, we developed a mathematical model examining the effects of five OXT receptor (OXTR) variants (V45L, P108A, L206V, V281M, and E339K) on OXT–OXTR binding dynamics in human embryonic kidney cells (HEK293T) and myometrial smooth muscle cells. The model was parameterized using experimentally derived, cell-specific OXTR surface localization measurements and literature-reported OXT-OXTR-binding kinetics. The model revealed differences in time to equilibrium between HEK293T and myometrial cells, distinct dynamics among genetic variants, and that early increases in OXT could partially rescue diminished responses in V281M and E339K variants. This model provides key insights into how genetic variants influence OXT dose responses and offers a framework for tailoring OXT dosing to patient-specific genetic profiles. |
| format | Article |
| id | doaj-art-c1a1adc5274c4c4290725da0a1a0d366 |
| institution | Kabale University |
| issn | 2948-1716 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Women's Health |
| spelling | doaj-art-c1a1adc5274c4c4290725da0a1a0d3662025-02-09T13:00:34ZengNature Portfolionpj Women's Health2948-17162025-02-013111210.1038/s44294-025-00058-yPredicting oxytocin binding dynamics in receptor genetic variants through computational modelingPreeti Dubey0Yingye Fang1K. Lionel Tukei2Shobhan Kuila3Xinming Liu4Annika Sahota5Antonina I. Frolova6Erin L. Reinl7Manasi Malik8Sarah K. England9Princess I. Imoukhuede10Department of Biomedical Engineering, University of WashingtonDepartment of Biomedical Engineering, University of WashingtonDepartment of Biomedical Engineering, University of WashingtonDepartment of Biomedical Engineering, University of WashingtonDepartment of Biomedical Engineering, University of WashingtonDepartment of Biomedical Engineering, University of WashingtonCenter for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU MedicineCenter for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU MedicineCenter for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU MedicineCenter for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU MedicineDepartment of Biomedical Engineering, University of WashingtonAbstract Approximately half of U.S. women giving birth annually receive Pitocin, a synthetic form of oxytocin (OXT), yet the optimal dosing remains challenging due to significant individual variability in response. To address this, we developed a mathematical model examining the effects of five OXT receptor (OXTR) variants (V45L, P108A, L206V, V281M, and E339K) on OXT–OXTR binding dynamics in human embryonic kidney cells (HEK293T) and myometrial smooth muscle cells. The model was parameterized using experimentally derived, cell-specific OXTR surface localization measurements and literature-reported OXT-OXTR-binding kinetics. The model revealed differences in time to equilibrium between HEK293T and myometrial cells, distinct dynamics among genetic variants, and that early increases in OXT could partially rescue diminished responses in V281M and E339K variants. This model provides key insights into how genetic variants influence OXT dose responses and offers a framework for tailoring OXT dosing to patient-specific genetic profiles.https://doi.org/10.1038/s44294-025-00058-y |
| spellingShingle | Preeti Dubey Yingye Fang K. Lionel Tukei Shobhan Kuila Xinming Liu Annika Sahota Antonina I. Frolova Erin L. Reinl Manasi Malik Sarah K. England Princess I. Imoukhuede Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling npj Women's Health |
| title | Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| title_full | Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| title_fullStr | Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| title_full_unstemmed | Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| title_short | Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| title_sort | predicting oxytocin binding dynamics in receptor genetic variants through computational modeling |
| url | https://doi.org/10.1038/s44294-025-00058-y |
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