Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures
Estetrol (E4), a natural estrogen produced by the human fetal liver, is actively studied for menopause and breast cancer treatment. It has low side effects and preferential estrogen receptor alpha (ER<i>α</i>) affinity. There are no data about its effects on endometriosis, a common gynec...
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MDPI AG
2023-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/4/1169 |
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| author | Daniel Patiño-García Jaime Palomino Cristián Pomés Claudia Celle Verónica Torres-Estay Renán Orellana |
| author_facet | Daniel Patiño-García Jaime Palomino Cristián Pomés Claudia Celle Verónica Torres-Estay Renán Orellana |
| author_sort | Daniel Patiño-García |
| collection | DOAJ |
| description | Estetrol (E4), a natural estrogen produced by the human fetal liver, is actively studied for menopause and breast cancer treatment. It has low side effects and preferential estrogen receptor alpha (ER<i>α</i>) affinity. There are no data about its effects on endometriosis, a common gynecological disease affecting 6–10% of cycling women, generating painful pelvic lesions and infertility. Current combined hormone treatment (progestins and estrogens) is safe and efficient; nevertheless, one-third of patients develop progesterone (P4) resistance and recurrence by reducing P4 receptors (PRs) levels. We aimed to compare E4 and 17<i>β</i>-estradiol (E2) effects using two human endometriotic cell lines (epithelial 11Z and stromal Hs832 cells) and primary cultures from endometriotic patients. We evaluated cell growth (MTS), migration (wound assay), hormone receptors levels (Western blot), and P4 response by PCR array. Compared to E2, E4 did not affect cell growth or migration but increased estrogen receptor alpha (ER<i>α</i>) and PRs, and reduced ER<i>β</i>. Finally, the incubation with E4 improved the P4 gene response. In conclusion, E4 increased PRs levels and genetic response without inducing cell growth or migration. These results suggest that E4 might be useful for endometriosis treatment avoiding P4 resistance; however, evaluating its response in more complex models is required. |
| first_indexed | 2024-03-11T05:13:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T05:13:15Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9dc8b73206024c6985cbf800a990af772023-11-17T18:27:28ZengMDPI AGBiomedicines2227-90592023-04-01114116910.3390/biomedicines11041169Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary CulturesDaniel Patiño-García0Jaime Palomino1Cristián Pomés2Claudia Celle3Verónica Torres-Estay4Renán Orellana5Departamento de Ciencias Químicas y Biológicas, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, General Gana 1702, Santiago 8370874, ChileEscuela de Medicina Veterinaria, Facultad de Ciencias Médicas, Universidad Bernardo O’Higgins, General Gana 1702, Santiago 8370874, ChileDivisión de Ginecología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8331150, ChileDivisión de Ginecología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8331150, ChileDepartamento de Ciencias Químicas y Biológicas, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, General Gana 1702, Santiago 8370874, ChileDepartamento de Ciencias Químicas y Biológicas, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, General Gana 1702, Santiago 8370874, ChileEstetrol (E4), a natural estrogen produced by the human fetal liver, is actively studied for menopause and breast cancer treatment. It has low side effects and preferential estrogen receptor alpha (ER<i>α</i>) affinity. There are no data about its effects on endometriosis, a common gynecological disease affecting 6–10% of cycling women, generating painful pelvic lesions and infertility. Current combined hormone treatment (progestins and estrogens) is safe and efficient; nevertheless, one-third of patients develop progesterone (P4) resistance and recurrence by reducing P4 receptors (PRs) levels. We aimed to compare E4 and 17<i>β</i>-estradiol (E2) effects using two human endometriotic cell lines (epithelial 11Z and stromal Hs832 cells) and primary cultures from endometriotic patients. We evaluated cell growth (MTS), migration (wound assay), hormone receptors levels (Western blot), and P4 response by PCR array. Compared to E2, E4 did not affect cell growth or migration but increased estrogen receptor alpha (ER<i>α</i>) and PRs, and reduced ER<i>β</i>. Finally, the incubation with E4 improved the P4 gene response. In conclusion, E4 increased PRs levels and genetic response without inducing cell growth or migration. These results suggest that E4 might be useful for endometriosis treatment avoiding P4 resistance; however, evaluating its response in more complex models is required.https://www.mdpi.com/2227-9059/11/4/1169endometriosisestetrolprogesteroneresistancehormones |
| spellingShingle | Daniel Patiño-García Jaime Palomino Cristián Pomés Claudia Celle Verónica Torres-Estay Renán Orellana Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures Biomedicines endometriosis estetrol progesterone resistance hormones |
| title | Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures |
| title_full | Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures |
| title_fullStr | Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures |
| title_full_unstemmed | Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures |
| title_short | Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures |
| title_sort | estetrol increases progesterone genetic response without triggering common estrogenic effects in endometriotic cell lines and primary cultures |
| topic | endometriosis estetrol progesterone resistance hormones |
| url | https://www.mdpi.com/2227-9059/11/4/1169 |
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