Background: Of the currently available treatment regimes for acromegaly, pegvisomant (PEG-V) has the highest efficacy. During PEG-V treatment, GH serum levels increase. The exact mechanism behind this is remains unclear. It could be explained by an ultra-short feedback loop via GH receptors in the anterior pituitary gland.
Objective: To assess the level of GH receptor (GHR) mRNA expression in somatotroph adenomas and to evaluate whether GHR blockade by PEG-V can lead to an increase in GH levels.
Design: In 32 somatotroph adenomas and 4 samples of human liver tissue after RNA extraction, mRNA expression of the full length GHR and d3GHR variant were assessed by real time PCR. After 24 and 72 h incubation with PEG-V, in different concentration (10−610−9 M), GH secretion was assessed in three primary GH-secreting cultures. With a two-site immunofluorometric assay having no cross-reaction with PEG-V GH concentrations were determined.
Results: In somatotroph adenomas, detectable levels of full length GHR and the d3GHR variant were found in 27 of 32 (84%) and in 23 of 32 (72%) cases respectively. GHR mRNA levels, full length and d3GHR, in the somatotroph adenomas amounted 0.8 and 4.8% of the expression level in human liver. The addition of PEG-V did not increase GH secretion by the cultured GH-secreting pituitary adenoma cells.
Conclusion: In human somatotroph pituitary adenomas the expression of GHR mRNA is low and PEG-V does not increase GH secretion in vitro. There was no relationship between expression of GHR in the adenoma and the effect of PEG-V. Therefore, the increase in GH level during PEG-V treatment in acromegaly patients seems not mediated by interference with an ultra-short feedback loop via GHR in the somatotroph adenoma, but rather via reduced feedback due to the lowered circulating IGF1 levels.
30 Apr - 04 May 2011
European Society of Endocrinology