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Free keywords:
acromegaly, pegvisomant, prolactin, GH4C1, pituitary adenoma
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
beta-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 mu g/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
mu g/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.
