Epidermal growth factor-binding sites, present in normal human and rat pituitaries, are absent in human pituitary adenomas.

Abstract

To investigate the involvement of epidermal growth factor (EGF) and its receptor in the pathogenesis of human pituitary adenomas, we examined the presence of EGF-binding sites in normal rat and human pituitaries and in human PRL- and GH-secreting and nonsecreting pituitary adenomas. Using crude membrane preparations, specific binding for [125I] EGF was found in normal rat and human pituitaries. Equilibrium was reached at 25 C in 40 min. There was no change in the Kd values between male rats [Kd, 0.65 +/- 0.35 nM (mean +/- SD)] and female rats (Kd, 0.51 +/- 0.15 nM), while the maximum capacity was significantly higher (P less than 0.05) in male rats (21 +/- 8 fmol/mg protein) than in female rats (10 +/- 2 fmol/mg protein). Scatchard analysis of the data suggested the presence of a single class of binding sites. In the three normal human pituitaries tested, specific [125I]EGF binding was also demonstrated. However, both the Kd and the maximum capacity varied widely. Twenty-two human pituitary adenomas were tested, but no specific binding was detected in any of them. In addition to the binding experiments, a radioreceptor assay using rat liver membranes was developed to detect EGF or EGF-like material in extracts of six human pituitary adenomas (two of each type). No EGF activity was detected in any of the extracts. From these results, we conclude that EGF-binding sites are present in normal pituitary tissue, suggesting a physiological role for EGF in this tissue. Consequently, the reason(s) for the lack of EGF binding in pituitary adenoma membranes is not known.