ArticleExperimental & molecular medicine2023
RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 19 citations in OpenAlex.
- ETS1-EGR2 facilitates renal cell carcinoma progression by activating NOTCH signalling.Clinical and translational medicine · 2026Article
- Estradiol-17β, a key embryonic signal, regulates gene expression and cellular functions in the porcine trophoblast.Biology of reproduction · 2026Article
- From microbes to milestones: Gut bacterial abundances and functional pathways associate with neurodevelopment following preterm birth.Gut microbiology · 2026Article
- [Development of an LC-MS/MS method for 32 steroid hormones and exploration of their gestational variations].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- HnRPD/AUF1 facilitates human ovarian cancer progression through activating FLI1 and maintaining cisplatin resistance.Molecular cancer · 2026Article
- Role of RGS12 in placental mitochondrial dysfunction and adverse pregnancy outcomes.Cellular and molecular life sciences : CMLS · 2026Article
- Role of ubiquitin‑proteasome system in preeclampsia (Review).Molecular medicine reports · 2026Review
- A head start: The relationship of placental factors to craniofacial and brain development.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Review
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- ARID1A restrains EMT and stemness of ovarian cancer cells through the Hippo pathway.International journal of oncology · 2024Article
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Production of estradiol (E2) by the placenta during human pregnancy ensures successful maintenance of placental development and fetal growth by stimulating trophoblast proliferation and the differentiation of cytotrophoblasts into syncytiotrophoblasts. Decreased levels of E2 are closely associated with obstetrical diseases such as preeclampsia (PE) in the clinic. However, the mechanisms underlying the inhibition of placental E2 biosynthesis remain poorly understood. Here, we report that regulator of G-protein signaling 2 (RGS2) affects E2 levels by regulating aromatase, a rate-limiting enzyme for E2 biosynthesis, by using human trophoblast-derived JEG-3 cells and human placental villus tissues. RGS2 enhanced the protein degradation of the transcription factor heart and neural crest derivatives expressed 1 (HAND1) by suppressing ubiquitin-specific protease 14 (USP14)-mediated deubiquitination of HAND1, resulting in the restoration of HAND1-induced trans-inactivation of the aromatase gene and subsequent increases in E2 levels. However, aromatase bound to RGS2 and repressed RGS2 GTPase activating protein (GAP) activity. Moreover, we observed a positive correlation between RGS2 and aromatase expression in clinical normal and preeclamptic placental tissues. Our results uncover a hitherto uncharacterized role of the RGS2-aromatase axis in the regulation of E2 production by human placental trophoblasts, which may pinpoint the molecular pathogenesis and highlight potential biomarkers for related obstetrical diseases.
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