1. In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells
- Author
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Thomas Cuny, Caroline Zeiller, Thomas Graillon, Dominique Figarella-Branger, Céline Defilles, Thierry Brue, Martin Bidlingmaier, Alain Enjalbert, Catherine Roche, Morgane Pertuit, Marily Theodoropoulou, Marie-Pierre Blanchard, Anne Barlier, figarella-branger, dominique, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany, APHM, Conception, Laboratory of Molecular Biology, Marseille, France, Department of Endocrinology [Munich], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and APHM Conception, Department of Endocrinology, Marseille, France *(T Brue and A Barlier contributed equally to this work)
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0301 basic medicine ,Male ,Cancer Research ,Endocrinology, Diabetes and Metabolism ,pituitary adenoma ,Growth hormone receptor ,0302 clinical medicine ,Endocrinology ,STAT5 Transcription Factor ,Tumor Cells, Cultured ,pegvisomant ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Chemistry ,Human Growth Hormone ,Middle Aged ,Growth hormone secretion ,3. Good health ,Somatostatin ,Oncology ,Female ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Adenoma ,Adult ,medicine.medical_specialty ,endocrine system ,prolactin ,Cell Survival ,030209 endocrinology & metabolism ,03 medical and health sciences ,Young Adult ,Pituitary adenoma ,Internal medicine ,Cell Line, Tumor ,PEG ratio ,Acromegaly ,medicine ,Animals ,Humans ,Aged ,Cell Proliferation ,GH4C1 ,Research ,Receptors, Somatotropin ,Janus Kinase 2 ,medicine.disease ,Rats ,030104 developmental biology ,Growth Hormone ,Pegvisomant ,acromegaly ,Growth Hormone-Secreting Pituitary Adenoma ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs (SSAs) and/or uncontrolled by transsphenoidal surgery. The residual GH-secreting tumor is therefore exposed to the action of circulating PEG. However, the biological effect of PEG at the pituitary level remains unknown. To assess the impact of PEG in vitro on the hormonal secretion (GH and prolactin (PRL)), proliferation and cellular viability of eight human GH-secreting tumors in primary cultures and of the rat somatolactotroph cell line GH4C1. We found that the mRNA expression levels of GHR were characterized in 31 human GH-secreting adenomas (0.086 copy/copy β-Gus) and the GHR was identified by immunocytochemistry staining. In 5/8 adenomas, a dose-dependent inhibition of GH secretion was observed under PEG with a maximum of 38.2±17% at 1μg/mL (PP
- Published
- 2016
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