Increased peripheral aromatase activity in prepubertal children with partial androgen insensitivity syndrome

It has been suggested that rate of estrogen formation was higher in patients with androgen insensitivity syndrome (AIS). This work was designed to find out if peripheral aromatase activity could be related to a defect in androgen action in prepubertal children with male pseudohermaphroditism. Fibroblast estrogen production was assayed by a highly specific enzymatic determination. Foreskin fibroblast strains were raised from 17 children with partial androgen insensitivity (PAIS) as defined by dihydrotestosterone binding activity in cells. Results are expressed as pmol estrogens/mg proteins synthetized/day when cultured fibroblasts are incubated with D4-androstenedione. In normal prepubertal boys (n = 19), aromatase activity ranged between 5 and 10 pmol estrogens/mg proteins/day, while in postpubertal boys it varied between 15 and 34 pmol estrogens/mg proteins/day. In prepubertal boys with PAIS (n = 17) aromatase activity is highly elevated: 19.4 +/- 8.4 pmol/mg proteins/day. These results show that (a) peripheral aromatase activity is low before puberty and (b) fibroblast estrogen synthesis is significantly (p less than 0.001) increased in prepubertal children with PAIS. Our data suggest that low utilization of androgens by target cells stimulates the production of estrogen. Peripheral aromatase activity can thus be considered as a 'marker' of androgen insensitivity in prepubertal children with male pseudohermaphroditism.