ArticleAmerican journal of physiology. Endocrinology and metabolism2010
SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of the KCNN3 gene.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- CaInternational journal of molecular sciences · 2023Review
- The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction.Reproductive biology and endocrinology : RB&E · 2022Article
- Transcriptional control of parturition: insights from gene regulation studies in the myometrium.Molecular human reproduction · 2021Review
- A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy.Cancers · 2019Article
- Intragenic Transcriptional cis-Antagonism Across SLC6A3.Molecular neurobiology · 2019Article
- Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.Pediatric research · 2017Article
- Chronic hypoxia upregulates DNA methyltransferase and represses large conductance Ca2+-activated K+ channel function in ovine uterine arteries.Biology of reproduction · 2017Article
- Silencing of voltage-gated potassium channel KV9.3 inhibits proliferation in human colon and lung carcinoma cells.Oncotarget · 2015Article
- Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes.American journal of reproductive immunology (New York, N.Y. : 1989) · 2014Article
- Gestational hypoxia increases reactive oxygen species and inhibits steroid hormone-mediated upregulation of Ca(2+)-activated K(+) channel function in uterine arteries.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Article
- Emerging role of the calcium-activated, small conductance, SK3 K+ channel in distal tubule function: regulation by TRPV4.PloS one · 2014Article
- Transforming growth factor β signaling in uterine development and function.Journal of animal science and biotechnology · 2014Review
- Chronic hypoxia inhibits pregnancy-induced upregulation of SKCa channel expression and function in uterine arteries.Hypertension (Dallas, Tex. : 1979) · 2013Article
- Isolation and characterization of the 5´-upstream region of the human voltage-gated Ca(2+) channel α 2δ-1 auxiliary subunit gene: promoter analysis and regulation by transcription factor Sp1.Pflugers Archiv : European journal of physiology · 2013Article
- Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population.Journal of perinatology : official journal of the California Perinatal Association · 2013Article
- Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium.Journal of cellular and molecular medicine · 2012Article
- Single-nucleotide polymorphisms in the KCNN3 gene associate with preterm birth.Reproductive sciences (Thousand Oaks, Calif.) · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of the small-conductance calcium-activated K(+) channel 3 (SK3) in transgenic mice compromises parturition, suggesting that the SK3 channel plays a role in pregnancy. In wild-type mouse myometrium, expression of SK3 transcript and protein is significantly reduced during pregnancy, but the mechanism(s) responsible for this attenuation of channel expression is unknown. The promoter region of the SK3-encoding mouse KCNN3 gene contains two binding sites for specificity protein (Sp) transcription factors, two of which are expressed in the uterus: Sp1, which enhances gene transcription in response to estrogen; and Sp3, which competes for the same binding motif as Sp1 and can repress gene expression. We investigated the hypothesis that Sp1 and Sp3 regulate SK3 channel expression during pregnancy. In mouse myometrium, Sp1 expression was reduced during late gestation, whereas Sp3 expression levels were constant throughout pregnancy. Using a reporter system, we found that Sp1 overexpression resulted in a significant increase in SK3 promoter activation and that Sp3 cotransfection reduced promoter activation to basal levels. These findings indicate that Sp3 outcompetes Sp1 to decrease SK3 transcription. To determine whether high levels of estrogen in vivo can affect the regulation of SK3 protein levels by Sp factors, ovariectomized mice were implanted with a 17β-estradiol or placebo pellet for 3 wk; estrogen-treated mice had reduced uterine SK3 protein expression compared with placebo-treated counterparts. In human myometrial cells overexpressing Sp1, estrogen treatment stimulated expression of the SK3 transcript. Overall, our findings indicate that Sp1 and Sp3 compete to regulate SK3 channel expression during pregnancy in response to stimulation by estrogen.
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