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

Abstract

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 beta-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 submembrane domain may be involved in the pathogenesis of GH secreting tumours, we studied this region in these tumours. 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. All samples exhibited normal migration patterns in the SSCP analysis which was further confirmed by direct DNA sequencing. 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.