ArticleThe Journal of clinical investigation2020
DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Clinical characteristics associated with somaticFrontiers in endocrinology · 2026Pooled it
- STING expression in pituitary neuroendocrine tumour immune microenvironments.Endocrine-related cancer · 2026Article
- Pathogenesis of nonfamilial somatotroph adenomas.The Journal of clinical endocrinology and metabolism · 2026Review
- Growth Hormone, Not Simply Just a Hormone for Growth.Endocrinology and metabolism (Seoul, Korea) · 2026Review
- Proteoformics-driven new concept of human growth hormone in clinical endocrinology.Frontiers in endocrinology · 2026Review
- Article
- Growth Hormone Signaling in Bladder Cancer: Transcriptomic Profiling of Patient Samples and In Vitro Evidence of Therapy Resistance via ABC Transporters and EMT Activation.International journal of molecular sciences · 2025Article
- Update on regulation of GHRH and its actions on GH secretion in health and disease.Reviews in endocrine & metabolic disorders · 2025Review
- New insights in cellular senescence: The pituitary model.Journal of neuroendocrinology · 2025Review
- Non-recurrent mutations and copy number changes predominate pituitary adenoma genomes.European journal of endocrinology · 2025Article
- Pituitary adenomas: biology, nomenclature and clinical classification.Reviews in endocrine & metabolic disorders · 2025Review
- Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.Journal of endocrinological investigation · 2025Article
- Somatic GNAS mutations in acromegaly: prevalence, clinical features and gender differences.Endocrine connections · 2025Article
- High level of aneuploidy and recurrent loss of chromosome 11 as relevant features of somatotroph pituitary tumors.Journal of translational medicine · 2024Article
- Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single-cell transcriptomics.Clinical and translational medicine · 2024Article
- Article
- Loss of PDE4D7 expression promotes androgen independence, neuroendocrine differentiation and alterations in DNA repair: implications for therapeutic strategies.British journal of cancer · 2023Article
- Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- Non-pituitary GH regulation of the tissue microenvironment.Endocrine-related cancer · 2023Article
- A worldwide bibliometric analysis of acromegaly in the past two decades: 1999-2022.Frontiers in neuroscience · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Drivers of sporadic benign pituitary adenoma growth are largely unknown. Whole-exome sequencing of 159 prospectively resected pituitary adenomas showed that somatic copy number alteration (SCNA) rather than mutation is a hallmark of hormone-secreting adenomas and that SCNAs correlate with adenoma phenotype. Using single-gene SCNA pathway analysis, we observed that both cAMP and Fanconi anemia DNA damage repair pathways were affected by SCNAs in growth hormone-secreting (GH-secreting) somatotroph adenomas. As somatotroph differentiation and GH secretion are dependent on cAMP activation and we previously showed DNA damage, aneuploidy, and senescence in somatotroph adenomas, we studied links between cAMP signaling and DNA damage. Stimulation of cAMP in C57BL/6 mouse primary pituitary cultures using forskolin or a long-acting GH-releasing hormone (GHRH) analog increased GH production and DNA damage measured by H2AX phosphorylation and a comet assay. Octreotide, a somatostatin receptor ligand that targets somatotroph adenoma GH secretion in patients with acromegaly, inhibited cAMP and GH and reversed DNA damage induction. In vivo long-acting GHRH treatment also induced pituitary DNA damage in mice. We conclude that cAMP, which induces somatotroph proliferation and GH secretion, may concomitantly induce DNA damage, potentially linking hormone hypersecretion to SCNA and genome instability. These results elucidating somatotroph adenoma pathophysiology identify pathways for targeted treatment.
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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.