In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells.
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 (P<0.0001 vs control). A dose-dependent inhibition of PRL secretion occurred in three mixed GH/PRL adenomas under PEG with a maximum of 52.8±11.5% at 10μg/mL (P<0.0001 vs control). No impact on proliferation of either human primary tumors or GH4C1 cell line was observed. We conclude that PEG inhibits the secretion of GH and PRL in primary cultures of human GH(/PRL)-secreting pituitary adenomas without effect on cell viability or cell proliferation.
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France.
Thomas
T
Cuny
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France.
Caroline
C
Zeiller
Endocrine Research UnitMedizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany.
Martin
M
Bidlingmaier
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France.
Céline
C
Défilles
APHMConception, Laboratory of Molecular Biology, Marseille, France.
Catherine
C
Roche
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France.
Marie-Pierre
MP
Blanchard
Department of EndocrinologyMax Planck Institute of Psychiatry, Munich, Germany.
Marily
M
Theodoropoulou
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France APHM TimoneDepartment of Neurosurgery, Marseille, France.
Thomas
T
Graillon
APHMConception, Laboratory of Molecular Biology, Marseille, France.
Morgane
M
Pertuit
APHM TimoneLaboratory of Neuropathology and Aix-Marseille University, INSERM, CRO2 UMR911, Marseille, France.
Dominique
D
Figarella-Branger
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France APHMConception, Laboratory of Molecular Biology, Marseille, France.
Alain
A
Enjalbert
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France APHM ConceptionDepartment of Endocrinology, Marseille, France.
Thierry
T
Brue
Aix-Marseille UniversityCNRS, CRN2M UMR7286, Marseille, France APHMConception, Laboratory of Molecular Biology, Marseille, France anne.barlier@univ-amu.fr.
Anne
A
Barlier
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D019382:Human Growth Hormone; D011388:Prolactin; D013006:Growth Hormone; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C406545:pegvisomant
GH4C1; acromegaly; pegvisomant; pituitary adenoma; prolactin