ArticleMolecular endocrinology (Baltimore, Md.)2013
Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas-New Potential Therapeutic Approach-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- The Role of Splicing Machinery as a Promising Potential Therapeutic Target for Pituitary Neuroendocrine Tumors (PitNETs).Cancers · 2026Review
- Aripiprazole alleviates the high prolactin levels induced by amisulpride via distinct molecular mechanisms: a network pharmacology and molecular docking study.BMC psychiatry · 2025Article
- Pituitary Tumorigenesis-Implications for Management.Medicina (Kaunas, Lithuania) · 2023Review
- Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature.Journal of medical case reports · 2023Review
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- 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
- The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas.BMC endocrine disorders · 2021Article
- Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms.Frontiers in endocrinology · 2021Review
- A Novel Mechanism Regulating Dopamine Receptor Type 2 Signal Transduction in Pituitary Tumoral Cells: The Role of cAMP/PKA-Induced Filamin A Phosphorylation.Frontiers in endocrinology · 2020Article
- The MAPK Pathway-Based Drug Therapeutic Targets in Pituitary Adenomas.Frontiers in endocrinology · 2019Review
- Transcriptome Analyses of Female Somatotropes and Lactotropes Reveal Novel Regulators of Cell Identity in the Pituitary.Endocrinology · 2018Article
- The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine.Endocrinology · 2018Article
- Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Functions of intrinsic disorder in transmembrane proteins.Cellular and molecular life sciences : CMLS · 2017Review
- Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.Endocrine · 2017Article
- Dopamine D2 receptors' effects on renal inflammation are mediated by regulation of PP2A function.American journal of physiology. Renal physiology · 2016Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R-/- mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.
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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 Socratic graph.