GPER1 is required to protect fetal health from maternal inflammation

Harding, Alfred T.; Goff, Marisa; Froggatt, Heather M.; Lim, Jean K.; Heaton, Nicholas S.

doi:10.1126/science.aba9001

Cited by 40 publications

(36 citation statements)

References 31 publications

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“…Similar results have been reported in airway inflammation [ 48 ]. In a very recent study, GPER1 was found necessary for the protection of reproductive and fetal tissues from IFN signaling in mice, suggesting a tissue-specific role [ 49 ]. However, ERα isoforms were not considered in these studies.…”

Section: Discussionmentioning

confidence: 99%

ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

Notas

Panagiotopoulos

Vamvoukaki

et al. 2021

IJMS

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Inflammation is important for the initiation and progression of breast cancer. We have previously reported that in monocytes, estrogen regulates TLR4/NFκB-mediated inflammation via the interaction of the Erα isoform ERα36 with GPER1. We therefore investigated whether a similar mechanism is present in breast cancer epithelial cells, and the effect of ERα36 expression on the classic 66 kD ERα isoform (ERα66) functions. We report that estrogen inhibits LPS-induced NFκB activity and the expression of downstream molecules TNFα and IL-6. In the absence of ERα66, ERα36 and GPER1 are both indispensable for this effect. In the presence of ERα66, ERα36 or GPER1 knock-down partially inhibits NFκB-mediated inflammation. In both cases, ERα36 overexpression enhances the inhibitory effect of estrogen on inflammation. We also verify that ERα36 and GPER1 physically interact, especially after LPS treatment, and that GPER1 interacts directly with NFκB. When both ERα66 and ERα36 are expressed, the latter acts as an inhibitor of ERα66 via its binding to estrogen response elements. We also report that the activation of ERα36 leads to the inhibition of breast cancer cell proliferation. Our data support that ERα36 is an inhibitory estrogen receptor that, in collaboration with GPER1, inhibits NFκB-mediated inflammation and ERα66 actions in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

Notas

Panagiotopoulos

Vamvoukaki

et al. 2021

IJMS

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“…While estrogens were traditionally thought to primarily regulate the female reproduction system, previous studies have demonstrated that estrogenic activity can regulate many pathways in the body, including immune responses [ 9 , 10 , 11 ]. In general, it is now appreciated that estrogens, and in particular E2, can control the proinflammatory signals/pathways of the immune system [ 12 , 13 , 14 ]. ERα and GPER1, two of the three known estrogen receptors that enact the observed effects of estrogens, are commonly associated with anti-inflammatory phenotypes [ 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection

Harding

Heaton

2022

Cancers

Self Cite

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Sex hormones, such as estrogen and testosterone, are steroid compounds with well-characterized effects on the coordination and development of vertebrate reproductive systems. Since their discovery, however, it has become clear that these “sex hormones” also regulate/influence a broad range of biological functions. In this review, we will summarize some current findings on how estrogens interact with and regulate inflammation and immunity. Specifically, we will focus on describing the mechanisms by which estrogens alter immune pathway activation, the impact of these changes during infection and the development of long-term immunity, and how different types of estrogens and their respective concentrations mediate these outcomes.

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“…GPER activity protects the fetus from maternal inflammation in mice ( 17 ). GPER promotes liver growth in zebrafish embryos and proliferation of cultured human primary hepatocytes ( 18 ).…”

Section: Membrane Estrogen Receptorsmentioning

confidence: 99%

The Interface of Nuclear and Membrane Steroid Signaling

Treviño

Gorelick

2021

Endocrinology

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Steroid hormones bind receptors in the cell nucleus and in the cell membrane. The most widely studied class of steroid hormone receptors are the nuclear receptors, named for their function as ligand-dependent transcription factors in the cell nucleus. Nuclear receptors, such as estrogen receptor alpha, can also be anchored to the plasma membrane, where they respond to steroids by activating signaling pathways independent of their function as transcription factors. Steroids can also bind integral membrane proteins, such as the G protein-coupled estrogen receptor. Membrane estrogen and progestin receptors have been cloned and characterized in vitro and influence the development and function of many organ systems. Membrane androgen receptors were cloned and characterized in vitro, but their function as androgen receptors in vivo is unresolved. We review the identity and function of membrane proteins that bind estrogens, progestins and androgens. We discuss evidence that membrane glucocorticoid and mineralocorticoid receptors exist, and whether glucocorticoid and mineralocorticoid nuclear receptors act at the cell membrane. In many cases, integral membrane steroid receptors act independently of nuclear steroid receptors, even though they may share a ligand.

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GPER1 is required to protect fetal health from maternal inflammation

Cited by 40 publications

References 31 publications

ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection

The Interface of Nuclear and Membrane Steroid Signaling

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