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. 2023 Jun 3;13:9046. doi: 10.1038/s41598-023-36146-9

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Proposed role of mERα-initiated signaling after treatment with physiological and supraphysiological doses of E2. In this study, it has been shown that the sensitivity to physiological E2 treatment is reduced in both non-reproductive tissues and uterus in the absence of mERα signaling. However, with a supraphysiological E2 dose, the effect in uterus is enhanced when mERα signaling is lacking. Therefore, we suggest that mERα signaling in general enhances E2 effects within the physiological range, and that it may also partially protect the uterus from potential harm of supraphysiological levels of E2. Created with BioRender.com.