ArticleEndocrinology2018
The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Spatial transcriptomics reveal PI3K-AKT and metabolic alterations in aggressive, treatment-resistant lactotroph pituitary neuroendocrine tumors.Acta neuropathologica communications · 2025Article
- Aripiprazole alleviates the high prolactin levels induced by amisulpride via distinct molecular mechanisms: a network pharmacology and molecular docking study.BMC psychiatry · 2025Article
- miR-21-5p Targets PIK3R1 to Regulate the NF-International journal of endocrinology · 2025Article
- Dopamine promotes osteogenic differentiation of PDLSCs by activating DRD1 and DRD2 during orthodontic tooth movement via ERK1/2 signaling pathway.Regenerative therapy · 2024Article
- ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway.Acta pharmacologica Sinica · 2022Article
- The dopaminergic control of Cushing's syndrome.Journal of endocrinological investigation · 2022Review
- Understanding the role of dopamine in cancer: past, present and future.Carcinogenesis · 2022Review
- Current and Emerging Medical Therapies in Pituitary Tumors.Journal of clinical medicine · 2022Review
- Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?Frontiers in endocrinology · 2022Review
- Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms.Frontiers in endocrinology · 2021Review
- Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.Stem cell research & therapy · 2020Article
- Prolactinomas Resistant to Treatment With Dopamine Agonists: Long-Term Follow-Up of Six Cases.Frontiers in endocrinology · 2018Article
- The Mechanism and Pathways of Dopamine and Dopamine Agonists in Prolactinomas.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Prolactin-secreting adenomas, or prolactinomas, cause hypogonadism, osteoporosis, and infertility. Although dopamine agonists (DAs) are used clinically to treat prolactinoma and reduce prolactin secretion via cAMP inhibition, the precise mechanism by which DAs inhibit lactotrope proliferation has not been defined. In this study, we report that phosphatidylinositol 3-kinase (PI3K) signals through AKT and mTOR to drive proliferation of pituitary somatolactotrope GH4T2 cells. We demonstrate that the DA cabergoline reduces activity of the mTOR effector s6K and diminishes GH4T2 cell proliferation primarily via activation of the long isoform of the dopamine D2 receptor (D2R). Dysfunctional D2R-mediated signaling and/or downregulated D2R expression is thought be the primary mechanism of DA resistance, which is observed in 10% to 20% of prolactinoma tumors. Dopamine-mediated D2R activation results in ERK stimulation and PI3K inhibition, suggesting that these two pathways act in an inverse manner to maintain lactotrope homeostasis. In this study, we found that ERK1/2-mediated prolactin transcription is inhibited by PI3K/CDK4-driven cell cycle progression, emphasizing that the ERK and PI3K signaling pathways oppose one another in lactotrope cells under homeostatic conditions. Lastly, we show that both ERK1/2 and AKT are activated in prolactinoma, demonstrating that the balance of ERK and AKT is dysregulated in human prolactinoma. Our findings reveal a potential use for dual pharmacological inhibitors of ERK and AKT as an alternative treatment strategy for DA-resistant prolactinomas.
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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.