A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis

Simple item page
dc.contributor.authorChadchan, S.B.
dc.contributor.authorPopli, P.
dc.contributor.authorLiao, Z.
dc.contributor.authorAndreas, E.
dc.contributor.authorDias, M.
dc.contributor.authorWang, T.
dc.contributor.authorGunderson, S.J.
dc.contributor.authorJimenez, P.T.
dc.contributor.authorLanza, D.G.
dc.contributor.authorLanz, R.B.
dc.contributor.authorFoulds, C.E.
dc.contributor.authorMonsivais, D.
dc.contributor.authorDeMayo, F.J.
dc.contributor.authorYalamanchili, H.K.
dc.contributor.authorJungheim, E.S.
dc.contributor.authorHeaney, J.D.
dc.contributor.authorLydon, J.P.
dc.contributor.authorMoley, K.H.
dc.contributor.authorO’Malley, B.W.
dc.contributor.authorKommagani, R.
dc.date.issued2024
dc.description.abstractCellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions.
dc.description.statementofresponsibilitySangappa B. Chadchan, Pooja Popli, Zian Liao, Eryk Andreas, Michelle Dias, Tianyuan Wang, Stephanie J.Gunderson, Patricia T. Jimenez, Denise G. Lanza, Rainer B. Lanz, Charles E. Foulds, Diana Monsivais, Francesco J. DeMayo, Hari Krishna Yalamanchili, Emily S. Jungheim, Jason D. Heaney, John P. Lydon, Kelle H. Moley, Bert W. O, Malley, Ramakrishna Kommagani
dc.identifier.citationNature Communications, 2024; 15(1):1947-1-1947-17
dc.identifier.doi10.1038/s41467-024-46180-4
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidAndreas, E. [0000-0001-8971-2343]
dc.identifier.urihttps://hdl.handle.net/2440/146628
dc.language.isoen
dc.publisherNature Portfolio
dc.rights© The Author(s) 2024. 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/.
dc.source.urihttp://dx.doi.org/10.1038/s41467-024-46180-4
dc.subjectEmbryonic induction; Hormone receptors; Reproductive biology
dc.subject.meshEndometrium
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshEndometriosis
dc.subject.meshSteroids
dc.subject.meshProgesterone
dc.subject.meshNeoplasm Proteins
dc.subject.meshReceptors, Steroid
dc.subject.meshReceptors, Progesterone
dc.subject.meshEstrogens
dc.subject.meshFemale
dc.titleA GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
dc.typeJournal article
pubs.publication-statusPublished online

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
hdl_146628.pdf
Size:
6.68 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Research Outputs