Evidence for a qualitative abnormality in the androgen receptor was obtained by studies of temperature sensitivity. The binding of [3H]dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) was studied in monolayers of cultured genital skin fibroblasts from genetic males with abnormal sexual differentiation resulting from androgen resistance. Binding in cells from eight patients with a female phenotype (complete and incomplete testicular feminization) fell from half-normal levels at the usual assay temperature of 37°C to levels <20% of normal when cells were incubated at 42°C. This thermal inactivation was rapidly reversed when the assay temperature was lowered to 37°C, was not associated with altered dihydrotestosterone metabolism, and was also demonstrable with [3H]methyltrienolone as the binding ligand. Binding increased to overlap the normal range when the assay temperature was lowered to 26°C. The patients with receptor-deficient testicular feminization include three pairs of siblings; the pedigrees in two of these families are compatible with X-linkage.
James E. Griffin