The IGF-I receptor sub-membrane domain is intact in GH-secreting pituitary tumours

BACKGROUND AND OBJECTIVE: Clinical acromegaly is characterized by dysregulation of somatotroph GH secretion in the presence of high circulating serum IGF-I levels. Physiologically, IGF-I exerts a negative feedback on GH secretion at both the hypothalamic and the pituitary levels. We have previously shown that the 943 and 950 tyrosine residues in the IGF-I receptor β-subunit are required for ligand signalling to the GH gene, as substitution of these residues abrogates IGF-I signal transduction. To determine whether a mutation within the IGF-I receptor sub-membrane domain may be involved in the pathogenesis of GH secreting tumours, we studied this region in these tumours. DESIGN: Exon 15 of the IGF-I receptor containing both the 943 and 950 tyrosines was analysed in 19 GH-secreting tumours by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Tumour DNA and patients' lymphocyte DNA, which served as normal controls, were analysed. RESULTS: All samples exhibited normal migration patterns in the SSCP analysis which was further confirmed by direct DNA sequencing. CONCLUSIONS: We conclude that mutations in the IGF-I receptor sub-membrane domain which disrupt the negative feedback loop are not involved in the pathogenesis of acromegaly.