Genital skin fibroblasts (GF) of patients with androgen insensitivity syndrome express higher insulin-like growth factor binding protein (IGFBP)-2,-3 and-5 than GF of normally virilized males

Background. We investigated the effects of androgens, estradiol (E-2) and insulin-like growth factor (IGF)-I on IGF-II, insulin-like growth factor binding protein (IGFBP)2, -3 and -5 and mRNA in genital fibroblasts (GF) from patients with complete androgen insensitivity (CAIS) and normally virilized males (C). Methods: Proteins were measured by specific RIA and Western ligand blot, and specific mRNA levels by RT-PCR normalized by GAPDH levels. Results: Secretion of IGF-II was lowered in CAIS (p < 0.001) GF and by testosterone + IGF-I in C GF. Secretion of IGFBP-2 was higher (p < 0.001) in CAIS GF and IGFBP-2 mRNA levels were increased by E-2 in C GF (p < 0.05). E-2 stimulated IGFBP-2,-3 and -5 expression in CAIS GF. CAIS GF also secreted more IGFBP-3 (p < 0.001) and accumulated 3-5 times more IGFBP-5 mRNA than C GF (p < 0.001). Conclusion: In contrast to C GF, the availability of IGF-II in CAIS GF is apparently decreased by two facts: by the decreased expression and by increased expression of IGFBP-2, -3 and -5. Furthermore, E-2 and IGF-I modulate the expression of IGF-II and IGFBP in GF. This may play a role in the failure to develop male external genitals in CAIS patients. Copyright (C) 2003 S. Karger AG, Basel.