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.