Defective Androgen Action at the Cellular Level in the Androgen Resistance Syndromes. I. Differences between the Complete and Incomplete Testicular Feminization Syndromes*

Publisher Website
Google Scholar
Abstract
5α-Dihydrotestosterone (DHT) cytosol binding, nuclear uptake of labeled DHT-receptor complexes, and DHT nuclear binding were studied in genital skin fibroblasts of normal individuals, three subjects with the complete testicular feminization syndrome (CTFS), and one patient with incomplete testicular feminization syndromes (ITFS). Cytosol receptor binding was assessed by cytosol incubations with [3H]DHT and analyzed by sucrose gradient centrifugation. Nuclear uptake was studied by using cytosol from normal and mutant fibroblasts incubated first with [3H]DHT and then with nuclei from normal and mutant fibroblasts. DHT nuclear binding was studied by incubating fibroblasts with [3H]DHT, and the nucleosol was analyzed by sucrose gradient centrifugation. An 8S specific androgenbinding cytosol protein was demonstrated in ITFS cells; however, a diminished amount of DHT binding was repeatedly noticed in mutant (ITFS) cells (5.8 fmol/mg protein) compared with that in normal cells (15.1 fmol/mg protein). No cytosol DHT binding was found in CTFS cells. A similar uptake of DHT-labeled normal cytosol was found in normal and mutant nuclei (disintegrations per min/αg DNA). A diminished nuclear uptake was found when the DHT-labeled cytosol was prepared from ITFS cells. No nuclear uptake was observed when the source of receptor was CTFS fibroblasts. A 3.5S DHT-binding nuclear protein was demonstrated in ITFS and normal cells; however, diminished DHT nuclear binding was noticed in ITFS cells (137 fmol/mg DNA) compared with that in normal cells (346 fmol/mg DNA). No nuclear DHT binding was found in CTFS cells. These data demonstrated the presence of specific 8S and 3.5S receptors at cytosol and nuclear levels, respectively, in ITFS. The presence of these macromolecules, although exhibiting diminished androgen binding, demonstrates that the underlying molecular abnormality in the patient with ITFS is different from that of the patient with CTFS.