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.

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas

“…27,31 Expression of EGFR was present at a low level in 5-10% of pituitary cells in one study. 28 In our study of normal pituitary, expression of EGFR, P-EGFR protein, and EGFR mRNA was detected.…”

“…In an earlier study of EGF-binding sites in pituitary adenomas using membrane-binding assays, Birman et al 31 reported that EGF-binding sites were present in normal human pituitary, but not in either functional or nonfunctional pituitary adenomas. However, subsequent studies using either immunohistochemistry or RT-PCR reported the presence of EGFR in pituitary adenomas with varying results.…”

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

“…However, it soon became evident that EGF is present in human corticotrophinomas and tends to correlate with invasiveness (39,43). EGF binding was detected in pituitary tumors, despite the initial negative autoradiography results (41,44,45). Semiquantitative reverse transcriptase PCR analysis and northern blot showed EGFR transcript in representatives of all pituitary tumor types, including all the assayed corticotrophinomas (38,41).…”

Expression of epidermal growth factor receptor in neoplastic pituitary cells: evidence for a role in corticotropinoma cells

“…Despite the fact that there is clear evidence of the presence of EGFr in the normal adenohypophysis (Chabot et al 1986, Fan & Childs 1995, the data concerning the expression of EGFr in pituitary tumors are still controversial (Ray & Melmed 1997, Dahia & Grossman 1999. Initial studies had failed to show any EGF binding sites in human pituitary adenomas (Birman et al 1987), while further investigations using immunohistochemical and RT-PCR approaches have described EGFr in pituitary adenomas, with one study demonstrating overexpression in most non-functional pituitary adenomas but absence in the hormone-secreting types (Chaidarun et al 1994), and another showing EGFr expression in all types of pituitary adenomas but at varying levels (LeRiche et al 1996). In the latter study, a positive correlation between EGFr expression and tumor aggressiveness was found.…”