In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells

Thomas Cuny (1) , Caroline Zeiller (1) , Martin Bidlingmaier (2) , Céline Défilles (1) , Catherine Roche (3) , Marie-Pierre Blanchard (1) , Marily Theodoropoulou (4) , Thomas Graillon (1) , Morgane Pertuit (3) , Dominique Figarella-Branger (5) , Alain Enjalbert (1) , Thierry Brue (1, 6) , Anne Barlier (1, 3)

1 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille
2 Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
3 APHM, Conception, Laboratory of Molecular Biology, Marseille, France
4 Department of Endocrinology [Munich]
5 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
6 APHM Conception, Department of Endocrinology, Marseille, France *(T Brue and A Barlier contributed equally to this work)

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 1 μg/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 10 μg/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.

Domains: Life Sciences [q-bio]; Human health and pathology

Thomas Cuny, Caroline Zeiller, Martin Bidlingmaier, Céline Défilles, Catherine Roche, et al.. In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells. Endocrine-Related Cancer, 2016, ⟨10.1530/ERC-16-0140⟩. ⟨hal-01478506⟩