Quantitative analysis of growth-related factors in human pituitary adenomas. Lowered insulin-like growth factor-I and its receptor mRNA in growth hormone-producing adenomas.

摘要

To elucidate the contribution of growth factors to the development, growth and behavior of human pituitary adenomas, the authors used competitive reverse transcription-polymerase chain reactions to quantify expression of mRNAs for growth factors extracted from pituitary adenomas. As previously diagnosed by endocrinologic evaluation, the pituitary adenomas in this study consisted of six prolactin-producing, six growth hormone (GH)-producing, four follicle-stimulating hormone producing and six nonfunctioning adenomas. The mRNAs examined included those for platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-I and -II; proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation; and pituitary-specific transcription factor-1 (Pit-1) which is a nuclear transcription factor expressed in the anterior pituitary. All factors except the last were expressed in all adenomas, and expression of PDGF B-chain, TGF-beta1, EGF, bFGF and IGF-II did not differ between the four adenoma varieties. Pit-1 was expressed only in GH- and prolactin-producing adenomas. PCNA expression also showed no differences. However, IGF-I mRNA in GH-producing adenomas was significantly lower than in prolactin-producing and nonfunctioning adenomas despite high serum IGF-I levels (1121+/-253 ng/ml). The analysis on IGF-I receptor mRNA was significantly lowered in GH-producing adenoma compared with the other types of adenoma. These findings suggest that the attenuation of negative feedback through the pituitary GH-IGF-I axis may be involved in development of GH-producing adenoma.