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

To elucidate the contribution of growth factors to the development, growth and behavior of human pituitary adenomas, the authors used competitive reve rse transcription-polymerase chain reactions to quantify expression of mRNA s for growth factors extracted from pituitary adenomas. As previously diagn osed by endocrinologic evaluation, the pituitary adenomas in this study con sisted 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)-beta 1, epidermal growth factor (EG F), basic fibroblast growth factor (bFGF) and insulin-like growth factor (I GF)-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 expressio n of PDGF B-chain, TGF-beta 1, EGF, bFGF and IGF-II did not differ between the four adenoma varieties. Pit-1 was expressed only in GH- and prolactin-p roducing 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 lowere d in GH-producing adenoma compared with the other types of adenoma, These f indings suggest that the attenuation of negative feedback through the pitui tary GH-IGF-I axis may be involved in development of GH-producing adenoma. (C) 1999 Elsevier Science B.V. All rights reserved.