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      Androgen Receptor Defects in Patients with Minimal and Partial Androgen Resistance Classified According to a Model of Androgen-Receptor Complex Energy States

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          We have characterized intracellularly the androgen-receptor (A-R) complexes formed by genital skin fibroblasts from 2 unrelated males with qualitative defects of the androgen receptor: one has a small nonhypospadic penis as part of a syndrome of mild androgen resistance; the other was born with ambiguous external genitalia. The dissociation rate constants of testosterone, methyltrienolone (MT), dihydrotestosterone (DHT) and mibolerone (MB) from normal androgen receptors were determined at various temperatures: when plotted by the method of Arrhenius, they yielded a linear hierarchy of dissociation states with energies of state IV > III > II > I, respectively. Relative to this hierarchy, patient A-R complexes were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. MB- or MT-R complexes of both patients were thermolabile; however, both up-regulated normally in response to prolonged incubation with either hormone. Apparent equilibrium affinity constants (K<sub>d</sub>) of the DHT- and MB-R complexes formed by both patients were normal; however, the binding capacity (B<sub>max</sub>) for MB in 1 case was subnormal. The distinctive biochemical phenotypes of A-R complexes in these 2 patients with androgen resistance will facilitate the definition of structure-function relations in the androgen receptor, a classical DNA-binding, transcription-regulating protein.

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          Author and article information

          Horm Res Paediatr
          Hormone Research in Paediatrics
          S. Karger AG
          02 December 2008
          : 33
          : 2-4
          : 87-94
          aLady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Centre for Human Genetics, McGill University, Montreal; bDivision of Endocrinology and Metabolism, University of Alberta, Edmonton, Canada
          181489 Horm Res 1990;33:87–94
          © 1990 S. Karger AG, Basel

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          Page count
          Pages: 8
          II. Hormone Action at the Receptor and Postreceptor Level


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