ArticleThe Journal of clinical endocrinology and metabolism2017
Tumor Necrosis Factor-α Impairs Kisspeptin Signaling in Human Gonadotropin-Releasing Hormone Primary Neurons.
Article in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Effects of CPAP on Testosterone Levels in Patients With Obstructive Sleep Apnea: A Meta-Analysis Study.Frontiers in endocrinology · 2019Pooled it
- Obesity, Oxidative Stress, and Inflammation in Precocious Puberty: Do All Roads Lead to the Hypothalamus?International journal of molecular sciences · 2026Review
- Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders.Andrology · 2026Review
- Cadmium Impairs Human GnRH Neuron Development: Mechanistic Insights into Reproductive Dysfunction.International journal of molecular sciences · 2026Article
- Hypothalamic neuroimmune remodeling as an immunometabolic bridge between childhood obesity and earlier pubertal onset.Frontiers in immunology · 2026Review
- The Role of Cytokines in the Development and Functioning of the Hypothalamic-Pituitary-Gonadal Axis in Mammals in Normal and Pathological Conditions.International journal of molecular sciences · 2025Review
- Testosterone and Obesity in an Aging Society.Biomolecules · 2025Review
- Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study.Reproductive biology and endocrinology : RB&E · 2025Article
- The dual burden of obesity: decoding metabolism and female reproductive endocrinology.Frontiers in physiology · 2025Review
- The Impact of the Endocrine and Immunological Function of Adipose Tissue on Reproduction in Women with Obesity.International journal of molecular sciences · 2024Review
- The kisspeptin system in and beyond reproduction: exploring intricate pathways and potential links between endometriosis and polycystic ovary syndrome.Reviews in endocrine & metabolic disorders · 2024Review
- Beyond the Metabolic Syndrome: Non-Obvious Complications of Obesity in Children.Children (Basel, Switzerland) · 2023Review
- Dietary trends and the decline in male reproductive health.Hormones (Athens, Greece) · 2023Review
- Association between the prevalence rates of circadian syndrome and testosterone deficiency in US males: data from NHANES (2011-2016).Frontiers in nutrition · 2023Article
- Sleep, testosterone and cortisol balance, and ageing men.Reviews in endocrine & metabolic disorders · 2022Review
- Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto-Placental Organ-on-Chip Platform.International journal of environmental research and public health · 2022Review
- Endocannabinoid System in the Neuroendocrine Response to Lipopolysaccharide-induced Immune Challenge.Journal of the Endocrine Society · 2022Review
- Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model.Amino acids · 2022Article
- Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism.International journal of molecular sciences · 2022Review
- Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion.Genes & development · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Context: Inflammatory pathways may impair central regulatory networks involving gonadotropin-releasing hormone (GnRH) neuron activity. Studies in humans are limited by the lack of human GnRH neuron cell lines. Objective: To establish an in vitro model of human GnRH neurons and analyze the effects of proinflammatory cytokines. Design: The primary human fetal hypothalamic cells (hfHypo) were isolated from 12-week-old fetuses. Responsiveness to kisspeptin, the main GnRH neurons' physiological regulator, was evaluated for biological characterization. Tumor necrosis factor alpha (TNF-α) was used as a proinflammatory stimulus. Main Outcome Measures: Expression of specific GnRH neuron markers by quantitative reverse transcription-polymerase chain reaction, flow cytometry, and immunocytochemistry analyses; and GnRH-releasing ability and electrophysiological changes in response to kisspeptin. Results: The primary hfHypo showed a high percentage of GnRH-positive cells (80%), expressing a functional kisspeptin receptor (KISS1R) and able to release GnRH in response to kisspeptin. TNF-α exposure determined a specific inflammatory intracellular signaling and reduced GnRH secretion, KISS1R expression, and kisspeptin-induced depolarizing effect. Moreover, hfHypo possessed a primary cilium, whose assembly was inhibited by TNF-α. Conclusion: The hfHypo cells represent a novel tool for investigations on human GnRH neuron biology. TNF-α directly affects GnRH neuron function by interfering with KISS1R expression and ciliogenesis, thereby impairing kisspeptin signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.