Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 26 P291

ECE2011 Poster Presentations Pituitary (111 abstracts)

GH receptor mRNA expression and the effect of pegvisomant on GH secretion by somatotroph pituitary adenomas

S J C M M Neggers 1 , M Bidlingmaier 3 , P M van Koetsveld 2 , R A Feelders 1 , D M Sprij-Mooij 2 , W W de Herder 1 , A J van der Lely 1 & L J Hofland 2


1Section Endocrinology, Department of Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands; 2Department of Medicine, Erasmus University and Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands; 3Klinikum der Ludwig-Maximilians Universität-Innenstadt, Muenchen, Germany.

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 (10−6–10−9 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.

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