Abstract
Mutations that cause androgen resistance by altering various properties of the androgen receptor other than its maximum binding capacity (Bmax) are termed receptor-positive (R+). We have studied intact pubic and genital skin fibroblasts (SF) from an XY infant with markedly ambiguous genitalia. Their androgen receptor activity had a Bmax of 20 fmol/mg protein (normal: 10–40), an equilibrium binding constant (Kd) of 0.7 nM (normal: ∼ 0.1), and failed to «up-regulate» in response to prolonged incubation with ∼ 3 nM MB (normal: 2- to 4-fold during 72 h). In addition, the mutant MB-receptor complexes dissociated with a half-life of 52 min at 33°C (normal: 300), and were more thermolabile than normal (<10% remained after 4 h at 42°C; normal: >50%). In contrast, the unliganded mutant receptor activity had a normal half-life (at 37°C, 10 h; at 42°C, 80 min). The aberrant properties were also demonstrable with 5α-dihydrotestosterone, or with a second synthetic ligand, methyltrienolone.
Conclusions: (i) these data reveal a severely defective R+ mutant androgen receptor that is distinct from any we have described heretofore (J Clin Endocrinol Metab 59: 679, 1984); (ii) the native mutant receptor does not misbehave until it is, or has been, bound to ligand; (iii) the latter suggests that free receptor molecules derived from mutant MB-receptor complexes differ from their never-liganded counterparts.
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Pinsky, L., Kaufman, M. & Leboeuf, G. 481 A NEW TYPE OF LIGAND-INDEPENDENT PARTIAL ANDROGEN RESISTANCE DETECTED WITH THE AID OF THE SYNTHETIC ANDROGEN , 17α-METHYL MIBOLERONE (MB). Pediatr Res 19, 191 (1985). https://doi.org/10.1203/00006450-198504000-00511
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DOI: https://doi.org/10.1203/00006450-198504000-00511