ArticleJournal of cellular and molecular medicine2021
Pro-inflammatory signals induce 20α-HSD expression in myometrial cells: A key mechanism for local progesterone withdrawal.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- An Ex Vivo Model for the Onset of Human Labor.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Transcription factors as essential regulators of myometrial smooth muscle cell function during pregnancy and labor.Cellular and molecular life sciences : CMLS · 2026Review
- The Pathophysiology of Spontaneous Preterm Birth: Emerging Mechanisms Reviewed by the Preterm Birth International Collaborative.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- M1 Macrophages Are a Source of IL-1α: A Driver of Progesterone Metabolism and Myometrial Contraction.Cells · 2025Article
- Elevated NGF provokes decidual lipid peroxidation and promotes preterm birth in mice.Journal of translational medicine · 2025Article
- Preterm Birth in African American Women: A Multi-Omic Pilot Study in Early Pregnancy.Biological research for nursing · 2025Article
- Variants of the Progesterone Receptor Gene as Modulators of Risk for Idiopathic Spontaneous Premature Birth.International journal of molecular sciences · 2025Article
- Article
- The hormonal control of parturition.Physiological reviews · 2024Review
- Progesterone inactivation in decidual stromal cells: A mechanism for inflammation-induced parturition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- BKCa channels are involved in spontaneous and lipopolysaccharide-stimulated uterine contraction in late gestation mice†.Biology of reproduction · 2024Article
- Regulation of 20α-Hydroxysteroid Dehydrogenase Expression in Term Pregnant Human Myometrium Ex Vivo.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- 20α-Hydroxysteroid Dehydrogenase Expression in the Human Myometrium at Term and Preterm Birth: Relationships to Fetal Sex and Maternal Body Mass Index.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Review
- The selective progesterone receptor modulator-promegestone-delays term parturition and prevents systemic inflammation-mediated preterm birth in mice.American journal of obstetrics and gynecology · 2022Article
- Spontaneous preterm birth: Involvement of multiple feto-maternal tissues and organ systems, differing mechanisms, and pathways.Frontiers in endocrinology · 2022Review
- Nuclear Receptors in Pregnancy and Outcomes: Clinical Perspective.Advances in experimental medicine and biology · 2022Article
- Article
- Pro-inflammatory signals induce 20α-HSD expression in myometrial cells: A key mechanism for local progesterone withdrawal.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Metabolism of progesterone (P4) by the enzyme 20α hydroxysteroid dehydrogenase (20α-HSD) in myometrial cells is postulated to be a mechanism for P4 withdrawal, which occurs concomitant to uterine inflammation (physiologic or infection-induced) and associated activation of transcription factors: NF-кB and AP-1, common to term and preterm labour. We found that 20α-HSD protein is significantly increased in human myometrium during term labour, and in mouse uterus during term and preterm labour. Treatment of human myometrial cells with the pro-inflammatory mediators, lipopolysaccharide (LPS, mimicking infection) and 12-O-tetradecanoylphorbol-13-acetate (TPA, mimicking inflammation), induced 20α-HSD gene expression and increased 20α-HSD protein abundance. LPS treatment decreased P4 release into the culture medium and resulted in up-regulation of GJA1 in the hTERT-HM cells. The NF-кB /AP-1 transcription factors mediated effects of LPS and TPA on 20α-HSD gene transcription. Both pro-inflammatory stimuli induced 20α-HSD promoter activity in LPS/TPA-treated cells which was significantly attenuated by inhibition of NF-кB (JSH: 20 µM) or AP-1 signalling (T5224: 10 µM). Deletion of NF-кB consensus sites abrogated LPS-mediated promoter induction, while removal of AP-1 sites reversed the TPA-mediated induction of 20α-HSD promoter. We conclude that inflammatory stimuli (physiologic or pathologic) that activate NF-кB or AP-1 induce 20α-HSD transcription and subsequent local P4 withdrawal resulting in up-regulation of GJA1 and activation of myometrium that precedes labour.
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