Abstract
Genital skin fibroblast strains have helped to identify heritable defects of the androgen-receptor system that cause androgen insensitivity (AI). Three quantitative types have been defined: receptor-negative1 (no or barely measurable androgen–receptor activity); receptor-deficient2,3 (easily measurable but less than normal); and receptor-positive4,5 (activity in the normal range: 15–50 fmol per mg protein). As the clinical extent of AI cannot be correlated with receptor activity, various qualitative receptor defects have been sought and found, including receptor thermolability6 and an increased rate of dissociation of androgen–receptor complexes7–9. We report here that normal human genital skin fibroblasts preincubated with 5α-dihydrotestosterone (DHT) for 19 h at 37 °C have twice as much DHT–receptor activity as unexposed replicates (basal). The increase is blocked by cycloheximide; thus it is a form of ‘up-regulation’ that is probably due to androgen-induced receptor synthesis. After DHT preincubation the fibroblasts from three subjects with three types of receptor-positive AI did not augment their basal activities. Such an aberrant response may underlie some cases of receptor-positive, steroid-resistant breast cancer in women10.
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Kaufman, M., Pinsky, L. & Feder-Hollander, R. Defective up-regulation of the androgen receptor in human androgen insensitivity. Nature 293, 735–737 (1981). https://doi.org/10.1038/293735a0
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DOI: https://doi.org/10.1038/293735a0
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