Purpose: Insulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion.
Methods: Cell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior.
Results: We found that IGF1 improves rat GH3 somatotroph cell viability via the PI3K/Akt/mTOR pathway and confirmed that IGF1 exerts a negative feedback on GH secretion by a transcriptional mechanism. We demonstrated that the negative IGF1 loop on GH secretion requires Akt activation that seems to play a pivotal role in the control of GH secretion. Furthermore, Akt activation is independent of PI3K and probably mediated by mTORC2. In addition, we found that Erk 1/2 is not involved in GH3 cell viability regulation, but may have a role in controlling GH secretion, independently of IGF1.
Conclusion: Our data confirm that mTOR inhibitors may be useful to reduce pituitary adenoma cell viability, while Erk 1/2 pathway may be considered as a useful therapeutic target to control GH secretion. Our results open the field for further studies searching for effective drugs to control GH hyper-secretion.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12020-017-1432-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments.
FASEB J
December 2024
Antibody and Vaccine Group, Faculty of Medicine, Centre for Cancer Immunology, School of Cancer Sciences, University of Southampton, Southampton, UK.
Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi-agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3-dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches.
View Article and Find Full Text PDFBioinformatics-based modeling of lung squamous cell carcinoma prognosis and prediction of immunotherapy response.
Discov Oncol
December 2024
Department Pulmonary and Critical Care Medicine, Tongde Hospital of Zhejiang Provincial, Hangzhou, China.
Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancer. It has a grim prognosis for patients, primarily because the disease often remains asymptomatic in its early stages. As a result, it is frequently diagnosed at an advanced stage, limiting treatment options.
View Article and Find Full Text PDFThe Integrin Receptors: From Discovery to Structure to Medicines.
Immunol Rev
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Innate immune cells perform vital tasks in detecting, seeking, and eliminating invading pathogens, thus ensuring host survival. However, loss of function of these cells or their overactive response to tissue injury often causes serious ailments. It is, therefore, crucial to understand at a basic level how these cells function in health and disease.
View Article and Find Full Text PDFComprehensive Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Data Unveils Sevoflurane-Induced Neurotoxicity Through SLC7A11-Associated Ferroptosis.
J Cell Mol Med
December 2024
Department of Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.
Sevoflurane's potential impact on cognitive function and neurodevelopment, especially in susceptible populations such as infants and the elderly, has raised widespread concern. This study focuses on how sevoflurane induces ferroptosis in astrocytes and identifies solute carrier family 7 member 11 (SLC7A11) as a mediator of ferroptosis, providing new insights into sevoflurane-related neurotoxic pathways. We analysed single-cell sequencing (scRNA-seq) data from sevoflurane-exposed mice and control mice, supplemented with bulk RNA-seq data, to assess gene expression alterations.
View Article and Find Full Text PDFCOMPOSIT study: evaluating osimertinib combination with targeted therapies in EGFR-mutated non-small cell lung cancer.
Oncologist
December 2024
Department of Pneumology and Thoracic Oncology, Tenon Hospital, Assistance Publique Hôpitaux de Paris and GRC 4, Theranoscan, Sorbonne Université, Paris, France.
Introduction: The emergence of diverse resistance mechanisms after osimertinib therapy, including on-target epidermal growth factor receptor (EGFR) mutations and off-target alterations, warrants investigation of novel therapeutics to overcome these challenges and improve patient outcomes.
Methods: COMPOSIT was a French, retrospective, multicenter, cohort study of the effectiveness and tolerability of osimertinib in combination with other targeted therapies in patients with advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) who harbored other oncogenic drivers as primary or acquired resistance mechanisms. Real-world progression-free survival (rwPFS), overall survival (OS), and objective response rate (ORR) were the primary endpoints.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!