ArticleThe Journal of clinical investigation2000
Direct regulation of pituitary proopiomelanocortin by STAT3 provides a novel mechanism for immuno-neuroendocrine interfacing.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Adaptation of the Porcine Pituitary Transcriptome, Spliceosome and Editome during Early Pregnancy.International journal of molecular sciences · 2023Pooled it
- From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis.Frontiers in neuroscience · 2026Review
- Characterization of prevalent genetic variants in the Estonian Biobank body-mass index GWAS.Nature communications · 2025Article
- Genetic models of Cushing's disease : From cells, in vivo transgenic models to human pituitary organoids.Pituitary · 2025Review
- Generation and purification of ACTH-secreting hPSC-derived pituitary cells for effective transplantation.Stem cell reports · 2023Article
- Review
- The Mechanisms Underlying Autonomous Adrenocorticotropic Hormone Secretion in Cushing's Disease.International journal of molecular sciences · 2020Review
- Cholecalciferol (Vitamin DMolecular neurobiology · 2019Article
- POMC: The Physiological Power of Hormone Processing.Physiological reviews · 2018Review
- Article
- To eat or not to eat: ontogeny of hypothalamic feeding controls and a role for leptin in modulating life-history transition in amphibian tadpoles.Proceedings. Biological sciences · 2018Article
- Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells.OncoTargets and therapy · 2017Article
- E2F1-mediated human POMC expression in ectopic Cushing's syndrome.Endocrine-related cancer · 2016Article
- Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.Nutrition & diabetes · 2016Article
- Hypothalamic leptin action is mediated by histone deacetylase 5.Nature communications · 2016Article
- Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Review
- STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.The Journal of clinical investigation · 2015Article
- STAT3 Target Genes Relevant to Human Cancers.Cancers · 2014Article
- Activation of the inflammatory transcription factor nuclear factor interleukin-6 during inflammatory and psychological stress in the brain.Journal of neuroinflammation · 2013Article
- STAT3 protein up-regulates Gα-interacting vesicle-associated protein (GIV)/Girdin expression, and GIV enhances STAT3 activation in a positive feedback loop during wound healing and tumor invasion/metastasis.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroendocrine ACTH secretion responds to peripheral inflammatory and stress signals. We previously demonstrated that the proinflammatory cytokine, leukemia inhibitory factor (LIF), affects the hypothalamo-pituitary-adrenal axis (HPA) by stimulating in vitro and in vivo pituitary proopiomelanocortin (POMC) gene expression and ACTH secretion and by potentiating the action of hypothalamic corticotropin releasing hormone (CRH). Whereas pathways shown thus far to regulate POMC expression exclusively involve cAMP or calcium, we here describe a direct and indirect STAT3-dependent regulation of POMC transcription by LIF. Using progressive 5'-deletions of POMC promoter, we identified a LIF-responsive -407/-301 region that contains two juxtaposed sequences within -399/-379 related to a STAT3 DNA-binding motif. Each sequence within -399/-379 separately corresponds to a low-affinity and direct binding site for STAT3, but, in combination, these sequences bind STAT3 cooperatively and with high affinity. Moreover, LIF-activated STAT3 indirectly mediates LIF corticotroph action by inducing and potentiating CRH-induced c-fos and JunB expression and binding to the POMC AP-1 element. We therefore conclude that both a direct and indirect route mediate LIF-induced STAT3 activation of POMC transcription. Demonstration of STAT3-dependent regulation of the POMC gene represents a powerful mechanism for immuno-neuroendocrine interfacing and implies a direct stimulation of ACTH secretion by inflammatory and stress-derived STAT3-inducing cytokines.
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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.