Establishment of procedures for studying mPR-interacting agents and physiological roles of mPR

Tokumoto, Toshinobu; Hossain, Md. Babul; Wang, Jun

doi:10.1016/j.steroids.2016.02.015

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…In immune cells, GPER expression on T cells has been shown to play a role in 17β-estradiol-induced thymic atrophy and autoimmune encephalomyelitis. PAQR7 is expressed in the reproductive and nervous systems ( Tokumoto et al, 2016 ), and in murine macrophages ( Lu et al, 2015 ) and in human T cells ( Dosiou et al, 2008 ), although the functional role of PAQR7 in those tissues remains relatively unclear. Given that the increased systemic estrogen and progesterone associated with pregnancy does not typically result in skin cancer or significant pathology in other tissues, we think it likely that the specific GPER and PAQR7 agonists will be well-tolerated.…”

Section: Discussionmentioning

confidence: 99%

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

Natale

Duperret

Zhang

et al. 2016

eLife

104

103

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The association between pregnancy and altered cutaneous pigmentation has been documented for over two millennia, suggesting that sex hormones play a role in regulating epidermal melanocyte (MC) homeostasis. Here we show that physiologic estrogen (17β-estradiol) and progesterone reciprocally regulate melanin synthesis. This is intriguing given that we also show that normal primary human MCs lack classical estrogen or progesterone receptors (ER or PR). Utilizing both genetic and pharmacologic approaches, we establish that sex steroid effects on human pigment synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). Activity of these receptors was activated or inhibited by synthetic estrogen or progesterone analogs that do not bind to ER or PR. As safe and effective treatment options for skin pigmentation disorders are limited, these specific GPER and PAQR7 ligands may represent a novel class of therapeutics.DOI: http://dx.doi.org/10.7554/eLife.15104.001

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Section: Discussionmentioning

confidence: 99%

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

Natale

Duperret

Zhang

et al. 2016

eLife

104

103

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“…They were subsequently identified in humans, but their localization in the plasma membrane has been debated and some studies suggest they reside in the endoplasmic reticulum instead (69–71). Five genetically distinct forms of mPRs are known, namely mPRα (PAQR7), mPRβ (PAQR8), mPRγ (PAQR5), mPRδ (PAQR6), and mPRε (PAQR9) (72). These receptors each have a seven-transmembrane domain structure that includes an extracellular P4-binding domain, which has high affinity but limited capacity for P4 binding (73).…”

Section: Receptor-mediated Actionsmentioning

confidence: 99%

Progesterone-Related Immune Modulation of Pregnancy and Labor

et al. 2019

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Pregnancy involves a complex interplay between maternal neuroendocrine and immunological systems in order to establish and sustain a growing fetus. It is thought that the uterus at pregnancy transitions from quiescent to laboring state in response to interactions between maternal and fetal systems at least partly via altered neuroendocrine signaling. Progesterone (P4) is a vital hormone in maternal reproductive tissues and immune cells during pregnancy. As such, P4 is widely used in clinical interventions to improve the chance of embryo implantation, as well as reduce the risk of miscarriage and premature labor. Here we review research to date that focus on the pathways through which P4 mediates its actions on both the maternal reproductive and immune system. We will dissect the role of P4 as a modulator of inflammation, both systemic and intrinsic to the uterus, during human pregnancy and labor.

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“…It has been shown that major mPRs are highly expressed in reproductive tissues [ 6 ] and function by coupling to G-proteins [ 7 ] to execute rapid non-genomic actions. Interestingly, homozygous mPR s mutant fish were generated but with no phenotype, suggesting redundancy among mPRs [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

CCM signaling complex (CSC) couples both classic and non-classic Progesterone receptor signaling

et al. 2022

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Background Breast cancer, the most diagnosed cancer, remains the second leading cause of cancer death in the United States, and excessive Progesterone (PRG) or Mifepristone (MIF) exposure may be at an increased risk for developing breast cancer. PRG exerts its cellular responses through signaling cascades involving classic, non-classic, or combined responses by binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs). Currently, the intricate balance and switch mechanisms between these two signaling cascades remain elusive. Three genes, CCM1-3, form the CCM signaling complex (CSC) which mediates multiple signaling cascades. Methods Utilizing molecular, cellular, Omics, and systems biology approaches, we analyzed the relationship among the CSC, PRG, and nPRs/mPRs during breast cancer tumorigenesis. Results We discovered that the CSC plays an essential role in coupling both classic and non-classic PRG signaling pathways by mediating crosstalk between them, forming the CmPn (CSC-mPRs-PRG-nPRs) signaling network. We found that mPR-specific PRG actions (PRG + MIF) play an essential role in this CmPn network during breast cancer tumorigenesis. Additionally, we have identified 4 categories of candidate biomarkers (9 intrinsic, 2 PRG-inducible, 1 PRG-repressive, 1 mPR-specific PRG-repressive, and 2 mPR-responsive) for Luminal-A breast cancers during tumorigenesis and have confirmed the prognostic application of RPL13 and RPL38 as intrinsic biomarkers using a dual validation method. Conclusions We have discovered that the CSC plays an essential role in the CmPn signaling network for Luminal-A breast cancers with identification of two intrinsic biomarkers.

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Establishment of procedures for studying mPR-interacting agents and physiological roles of mPR

Cited by 20 publications

References 34 publications

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

Progesterone-Related Immune Modulation of Pregnancy and Labor

CCM signaling complex (CSC) couples both classic and non-classic Progesterone receptor signaling

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