ArticleDigestive diseases and sciences2013
Chronic estrogen deficiency causes gastroparesis by altering neuronal nitric oxide synthase function.
Article in Digestive diseases and sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Prevalence and predictors of small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis.Journal of gastroenterology · 2018Pooled it
- Aryl hydrocarbon receptor deficiency leads to sex- and age-dependent colonic dysmotility in mice.Journal of physiology and biochemistry · 2026Article
- Gender differences in symptoms suggestive of diabetic gastroparesis in the West Bank: clinical insights from a cross-sectional study.Frontiers in medicine · 2026Article
- Sex-specific epigenetics drive low GPER expression in gastrointestinal smooth muscles in type 2 diabetic mice.Scientific reports · 2024Article
- The Association between Hormone Replacement Therapy and Gastroparesis in Post-Menopausal Women: A Worldwide Database Analysis.Journal of personalized medicine · 2024Article
- Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.BMC gastroenterology · 2024Article
- Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- 17β-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic Female Mice.Antioxidants (Basel, Switzerland) · 2023Article
- Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Nitric Oxide Regulates Estrus Cycle Dependent Colonic Motility in Mice.Frontiers in neuroscience · 2021Article
- Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle.Frontiers in pharmacology · 2021Article
- Article
- Inhibition of GSK-3β restores delayed gastric emptying in obesity-induced diabetic female mice.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model.BMC gastroenterology · 2020Article
- Gastric Biopsies in Gastroparesis: Insights into Gastric Neuromuscular Disorders to Aid Treatment.Gastroenterology clinics of North America · 2020Review
- Activation of Nrf2 attenuates delayed gastric emptying in obesity induced diabetic (T2DM) female mice.Free radical biology & medicine · 2019Article
- Gastroparesis.Nature reviews. Disease primers · 2018Review
- Estrogen relaxes gastric muscle cells via a nitric oxide- and cyclic guanosine monophosphate-dependent mechanism: A sex-associated differential effect.Experimental and therapeutic medicine · 2018Article
- Lactulose Hydrogen Breath Test Result Is Associated with Age and Gender.BioMed research international · 2016Article
- Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats.The Journal of reproduction and development · 2015Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGastroparesis affects predominantly females; however, the biological basis for this gender bias is completely unknown. Several lines of evidence suggest that nitrergic dependent stomach motility function is reduced in diabetic gastroparesis and that nNOS is estrogen-regulated.
aimsThe purpose of this study was to investigate whether reduced levels of estradiol-17β (E2) down-regulates tetrahydrobiopterin (BH4, a cofactor for nNOS dimerization and enzyme activity) biosynthesis and therefore nNOS mediated gastric motility would be impaired in a mouse model of chronic estrogen deficiency, follicle stimulating hormone receptor knock-out female mice (FORKO).
methodsIn-bred 12-week-old female FORKO mice were obtained from our FORKO breeding colony. Gastric emptying was measured in overnight fasting mice. Nitrergic relaxation (AUC/mg tissue) was measured at 2 Hz through electric field stimulation using gastric antrum strips prepared from WT and FORKO mice. Protein expression for nNOSα, BH4 biosynthesis enzymes (GCH-1, DHFR) and estrogen receptors (α, β) were measured in gastric antrum by western blotting. Levels of BH4 and oxidized BH2, B biopterin levels were determined by HPLC.
resultsIn FORKO, compared to wild type (WT) stomachs we indentified (1) reduced (%) gastric emptying (64 ± 2.5 vs. 77.6 ± 0.88), (2) greater reduction in nitregic relaxation (-0.13 ± 0.012 vs. -0.28 ± 0.012), (3) increased nNOS dimerization (0.48 ± 0.02 vs. 0.34 ± 0.05), (4) decreased NO release whether measured at 24 h (0.6 ± 0.04 vs. 1.7 ± 0.22, p < 0.05) or at 48 h (3.4 ± 0.26 vs. 5.0 ± 0.15, p < 0.05) of incubation, (5) decreased GCH-1 (1.9 ± 0.06 vs. 2.3 ± 0.04), DHFR (1.8 ± 0.14 vs. 2.4 ± 0.07) and ERα (2.7 ± 0.4 vs. 3.9 ± 0.4) and (6) increased oxidized biopterin levels and decreased ratio of BH4 versus BH2 + B.
conclusionWe conclude that chronic estrogen deficiency negatively modifies the function of both BH4 and nNOS thereby contributing to the development of gastroparesis in a FORKO mouse model.
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