Morris Kaufman, Leonard Pinsky, Bruce Gottlieb, Mark Trifiro
{"title":"正常和突变雄激素受体复合物在人生殖器皮肤成纤维细胞中的状态转变","authors":"Morris Kaufman, Leonard Pinsky, Bruce Gottlieb, Mark Trifiro","doi":"10.1016/0022-4731(90)90184-T","DOIUrl":null,"url":null,"abstract":"<div><p>We have incubated cells from controls and subjects with receptor-defective androgen resistance with <sup>3</sup>H-labelled testosterone (T), methyltrienolone (MT), dihydrotestos-terone (DHT) or mibolerone (MB) and studied the temperature dependance of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV > III > II > I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90184-T","citationCount":"1","resultStr":"{\"title\":\"The state transitions of normal and mutant androgen-receptor complexes in human genital skin fibroblasts\",\"authors\":\"Morris Kaufman, Leonard Pinsky, Bruce Gottlieb, Mark Trifiro\",\"doi\":\"10.1016/0022-4731(90)90184-T\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>We have incubated cells from controls and subjects with receptor-defective androgen resistance with <sup>3</sup>H-labelled testosterone (T), methyltrienolone (MT), dihydrotestos-terone (DHT) or mibolerone (MB) and studied the temperature dependance of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV > III > II > I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors.</p></div>\",\"PeriodicalId\":17138,\"journal\":{\"name\":\"Journal of steroid biochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1990-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/0022-4731(90)90184-T\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of steroid biochemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/002247319090184T\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of steroid biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/002247319090184T","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The state transitions of normal and mutant androgen-receptor complexes in human genital skin fibroblasts
We have incubated cells from controls and subjects with receptor-defective androgen resistance with 3H-labelled testosterone (T), methyltrienolone (MT), dihydrotestos-terone (DHT) or mibolerone (MB) and studied the temperature dependance of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV > III > II > I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors.