Growth hormone receptor mRNA expression in non-functioning and somatotroph pituitary adenomas: implications for growth hormone substitution therapy?

Abstract

The use of growth hormone (GH) in patients with GH deficiency induced by pituitary adenoma is widely accepted, but the safety of this mitogenic hormone, particularly in patients with residual tumor after neurosurgery, continues to be a concern. Since the mitogenic potency of GH is dependent upon the presence of the GH receptor (GH-R) and the subsequent IGF-1/IGF receptor (IGF-1-R) system we investigated the expression of the members of the growth hormone cascade in endocrine inactive and GH-producing pituitary adenomas. Tissue specimens of 18 clinically non-functioning pituitary adenomas and 6 GH-producing adenomas were collected following transsphenoidal surgery while normal cadaver pituitary glands served as controls. After RNA extraction, semi-quantitative RT-PCR amplification with specific primers for GH, GH-R, IGF-1 and IGF-1-R was performed. Applying this sensitive RT-PCR based approach, GH-R expression was demonstrated in all normal pituitaries, most inactive adenomas (94%), and the majority of GH-producing adenomas (66%). Both IGF-1 and IGF-1-R mRNA was detectable in the majority of inactive (72% and 77%, respectively) and somatotrophic adenomas (83% and 83%). While IGF-1-R mRNA was expressed in all normal pituitary specimen studied, IGF-1 was detectable in only 55% of them. In summary, expression of members of the GH-IGF-1 cascade could be demonstrated in a substantial subset of patients with non-functioning and GH-producing pituitary adenomas. These factors might serve as a substrate for the transduction of mitogenic effects of GH on remnant pituitary tumors during GH replacement therapy. Therefore, GH therapy should be carefully considered and patients on GH therapy kept under close observation.